Methyl 3-[3-(ethoxy­carbon­yl)thio­ureido]-1H-pyrazole-5-carboxyl­ate

Huang, B.; Kung, P.-P.; Rheingold, A.L.; DiPasquale, A.; Yanovsky, A.

doi:10.1107/S1600536809016742

organic compounds

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Volume 65| Part 6| June 2009| Page o1249

doi:10.1107/S1600536809016742

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Methyl 3-[3-(ethoxycarbonyl)thioureido]-1H-pyrazole-5-carboxylate

Buwen Huang,^a Pei-Pei Kung,^a Arnold L. Rheingold,^b Antonio DiPasquale ^b and Alex Yanovsky ^a ^*

^aPfizer Global Research and Development, La Jolla Labs, 10770 Science Center Drive, San Diego, CA 92121, USA, and ^bDepartment of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
^*Correspondence e-mail: alex.yanovsky@pfizer.com

(Received 1 May 2009; accepted 4 May 2009; online 14 May 2009)

The title compound, C₉H₁₂N₄O₄S, was proven to be the product of the reaction of methyl 5-amino-1H-pyrazole-3-carboxylate with ethyl isothiocyanatocarbonate. All non-H atoms of the molecule are planar, the mean deviation from the least squares plane being 0.048 Å. The intramolecular N—H⋯O bond involving the NH-group, which links the thiourea and pyrazole fragments, closes a six-membered pseudo-heterocyclic ring, and two more hydrogen bonds (N—H⋯O with the participation of the pyrazole NH group and N—H⋯S involving the second thiourea NH group) link the molecules into infinite chains running along [1 $[\overline{2}]$ 0].

Related literature

For the structures of similar N-pyrazole-substituted thiourea derivatives, see: Pask et al. (2006 ); Wen et al. (2006 ).

Experimental

Crystal data

C₉H₁₂N₄O₄S
M_r = 272.29
Triclinic, $[P \overline 1]$
a = 8.0855 (8) Å
b = 9.0035 (8) Å
c = 9.5959 (9) Å
α = 64.510 (1)°
β = 82.294 (1)°
γ = 78.716 (1)°
V = 617.39 (10) Å³
Z = 2
Mo Kα radiation
μ = 0.28 mm⁻¹
T = 208 K
0.20 × 0.15 × 0.10 mm

Data collection

Siemens P4 diffractometer with APEX CCD detector
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.947, T_max = 0.973
5852 measured reflections
2653 independent reflections
2255 reflections with I > 2σ(I)
R_int = 0.044

Refinement

R[F² > 2σ(F²)] = 0.040
wR(F²) = 0.113
S = 1.04
2653 reflections
166 parameters
H-atom parameters constrained
Δρ_max = 0.39 e Å⁻³
Δρ_min = −0.28 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯S1ⁱ	0.87	2.51	3.347 (1)	161
N2—H2⋯O2	0.87	1.92	2.657 (2)	141
N4—H4⋯O3ⁱⁱ	0.87	2.03	2.876 (2)	164
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) -x+2, -y-1, -z+1.

Data collection: SMART (Bruker, 1997 ); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: ORTEP-32 (Farrugia, 1997 ); software used to prepare material for publication: WinGX (Farrugia, 1999 ).

Supporting information

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536809016742/dn2451sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809016742/dn2451Isup2.hkl

checkCIF report

Comment top

The reaction of methyl 5-amino-1H-pyrazole-3-carboxylate with ethyl isothiocyanatocarbonate produces the pyrazole-thiourea deivative; its structure was established by the present X-ray study (Fig.1).

All non-H atoms of the molecule are planar (mean deviation from its least squares plane is 0.048 Å), in contrast to previously studied pyrazole-thiourea derivative (Wen et al., 2006), where the pyrazole fragment has a nitrile substituent in position 4 and pyrazole/thiourea fragments form dihedral angle of 46.2°. Another similar compound, where pyrazole has no substituents in position 4 (Pask et al., 2006), is also essentially planar, just like the title compound.

There are three NH-groups in the molecule which are responsible for the formation of three independent H-bonds in the crystal (Table 2). The intramolecular N2—H2···O2 bond closes the 6-membered pseudo-cycle, whereas two intermolecular H-bonds each produce typical centrosymmmetric pairing motive, and their combination thus gives rise to infinite chains running along the [1,-2,0]. direction in the crystal (Fig. 2).

Related literature top

For the structures of similar N-pyrazole-substituted thiourea derivatives, see: Pask et al. (2006); Wen et al. (2006).

Experimental top

A suspension of methyl 5-amino-1H-pyrazole-3-carboxylate (2.0 g, 14.2 mmol) in 10 ml of ethyl acetate and 40 ml of benzene was cooled to 0°C and stirred. To this solution, ethyl isothiocyanatocarbonate (2.04 g, 15.6 mmol) in 10 ml benzene was added dropwise. The resulting reaction mixture was allowed to warm up to room temperature, and stirring was continued for 5 h. The reaction mixture was filtered, and washed with plenty of ether to afford the desired product (3.32 g, 12.2 mmol, 86.0% yield). ¹H NMR (400 MHz, DMSO-d₆) δ p.p.m.: 13.99 (br. s., 1 H), 12.12 (br. s., 1 H), 11.48 (br. s., 1 H), 7.51 (s, 1 H), 4.22 (q, J=7.07 Hz, 2 H), 3.85 (s, 3 H), 1.26 (t, J=7.07 Hz, 3 H).

Computing details top

Data collection: SMART (Bruker, 1997); cell refinement: SAINT (Bruker, 1997); data reduction: SAINT (Bruker, 1997); program(s) used to solve structure: SIR2004 (Burla et al., 2005); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-32 (Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures top

	Fig. 1. Molecular structure of the title compound showing 50% probability displacement ellipsoids and atom numbering scheme; H atoms are drawn as circles with arbitrary small radius.
	Fig. 2. Packing diagram for the title compound viewed approximately along the a axis; H-bonds are shown as dashed lines.

Methyl 3-[3-(ethoxycarbonyl)thioureido]-1H-pyrazole-5-carboxylate top

Crystal data top

C₉H₁₂N₄O₄S	Z = 2
M_r = 272.29	F(000) = 284
Triclinic, P1	D_x = 1.465 Mg m⁻³
Hall symbol: -P 1	Mo Kα radiation, λ = 0.71073 Å
a = 8.0855 (8) Å	Cell parameters from 3767 reflections
b = 9.0035 (8) Å	θ = 2.5–27.8°
c = 9.5959 (9) Å	µ = 0.28 mm⁻¹
α = 64.510 (1)°	T = 208 K
β = 82.294 (1)°	Block, colorless
γ = 78.716 (1)°	0.20 × 0.15 × 0.10 mm
V = 617.39 (10) Å³

Data collection top

Siemens P4 diffractometer with APEX CCD	2653 independent reflections
Radiation source: fine-focus sealed tube	2255 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.044
ϕ and ω scans	θ_max = 28.2°, θ_min = 2.4°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −5→10
T_min = 0.947, T_max = 0.973	k = −11→11
5852 measured reflections	l = −11→12

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F² > 2σ(F²)] = 0.040	H-atom parameters constrained
wR(F²) = 0.113	w = 1/[σ²(F_o²) + (0.0521P)² + 0.1805P] where P = (F_o² + 2F_c²)/3
S = 1.04	(Δ/σ)_max = 0.001
2653 reflections	Δρ_max = 0.39 e Å⁻³
166 parameters	Δρ_min = −0.28 e Å⁻³
0 restraints	Extinction correction: SHELXL (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.064 (8)

Crystal data top

C₉H₁₂N₄O₄S	γ = 78.716 (1)°
M_r = 272.29	V = 617.39 (10) Å³
Triclinic, P1	Z = 2
a = 8.0855 (8) Å	Mo Kα radiation
b = 9.0035 (8) Å	µ = 0.28 mm⁻¹
c = 9.5959 (9) Å	T = 208 K
α = 64.510 (1)°	0.20 × 0.15 × 0.10 mm
β = 82.294 (1)°

Data collection top

Siemens P4 diffractometer with APEX CCD	2653 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	2255 reflections with I > 2σ(I)
T_min = 0.947, T_max = 0.973	R_int = 0.044
5852 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.040	0 restraints
wR(F²) = 0.113	H-atom parameters constrained
S = 1.04	Δρ_max = 0.39 e Å⁻³
2653 reflections	Δρ_min = −0.28 e Å⁻³
166 parameters

Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.

Refinement. Refinement of F² against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F², conventional R-factors R are based on F, with F set to zero for negative F². The threshold expression of F² > σ(F²) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F² are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
C1	0.7861 (3)	0.9454 (2)	−0.0198 (2)	0.0539 (6)
H1A	0.6653	0.9725	−0.0320	0.081*
H1B	0.8446	1.0106	−0.1156	0.081*
H1C	0.8125	0.9706	0.0626	0.081*
C2	0.8414 (3)	0.7653 (2)	0.0194 (2)	0.0451 (5)
H2A	0.8135	0.7375	−0.0619	0.054*
H2B	0.9638	0.7366	0.0301	0.054*
C3	0.7832 (2)	0.5090 (2)	0.22047 (19)	0.0319 (4)
C4	0.6784 (2)	0.27556 (19)	0.44802 (18)	0.0285 (4)
C5	0.7965 (2)	−0.00499 (19)	0.46055 (19)	0.0300 (4)
C6	0.7316 (2)	−0.1229 (2)	0.5968 (2)	0.0310 (4)
H6	0.6562	−0.1048	0.6734	0.037*
C7	0.8050 (2)	−0.2725 (2)	0.59165 (19)	0.0312 (4)
C8	0.7909 (2)	−0.4462 (2)	0.6958 (2)	0.0328 (4)
C9	0.6497 (3)	−0.6292 (2)	0.9141 (2)	0.0435 (5)
H9A	0.6341	−0.6894	0.8550	0.065*
H9B	0.5509	−0.6267	0.9831	0.065*
H9C	0.7486	−0.6844	0.9741	0.065*
N1	0.69023 (19)	0.44206 (16)	0.35749 (16)	0.0322 (3)
H1	0.6316	0.5127	0.3917	0.039*
N2	0.77543 (19)	0.16936 (16)	0.39615 (16)	0.0327 (3)
H2	0.8340	0.2152	0.3099	0.039*
N3	0.9003 (2)	−0.07384 (17)	0.37579 (17)	0.0360 (4)
N4	0.9033 (2)	−0.23814 (17)	0.46052 (17)	0.0344 (3)
H4	0.9626	−0.3141	0.4333	0.041*
O1	0.75193 (17)	0.67399 (14)	0.16595 (14)	0.0374 (3)
O2	0.87813 (18)	0.43041 (15)	0.15826 (15)	0.0425 (3)
O3	0.87755 (18)	−0.56425 (14)	0.67884 (15)	0.0407 (3)
O4	0.67259 (17)	−0.46002 (15)	0.80911 (15)	0.0397 (3)
S1	0.54880 (6)	0.22717 (5)	0.60563 (5)	0.03395 (17)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0681 (15)	0.0334 (10)	0.0449 (11)	−0.0077 (10)	0.0106 (10)	−0.0060 (8)
C2	0.0512 (12)	0.0338 (9)	0.0352 (9)	−0.0029 (8)	0.0133 (8)	−0.0061 (8)
C3	0.0347 (9)	0.0267 (8)	0.0311 (8)	0.0000 (7)	0.0010 (7)	−0.0119 (6)
C4	0.0312 (9)	0.0247 (7)	0.0300 (8)	0.0008 (6)	−0.0025 (7)	−0.0137 (6)
C5	0.0340 (9)	0.0240 (8)	0.0333 (8)	0.0005 (6)	−0.0013 (7)	−0.0154 (7)
C6	0.0343 (9)	0.0257 (8)	0.0346 (8)	0.0005 (6)	0.0007 (7)	−0.0171 (7)
C7	0.0346 (9)	0.0259 (8)	0.0359 (9)	−0.0010 (7)	−0.0003 (7)	−0.0174 (7)
C8	0.0356 (9)	0.0295 (8)	0.0373 (9)	−0.0036 (7)	0.0003 (7)	−0.0189 (7)
C9	0.0499 (12)	0.0310 (9)	0.0460 (11)	−0.0095 (8)	0.0089 (9)	−0.0147 (8)
N1	0.0393 (8)	0.0234 (7)	0.0306 (7)	−0.0001 (6)	0.0074 (6)	−0.0127 (6)
N2	0.0405 (8)	0.0234 (7)	0.0313 (7)	−0.0012 (6)	0.0061 (6)	−0.0124 (6)
N3	0.0436 (9)	0.0251 (7)	0.0383 (8)	−0.0008 (6)	0.0038 (7)	−0.0160 (6)
N4	0.0403 (9)	0.0256 (7)	0.0396 (8)	−0.0003 (6)	0.0042 (7)	−0.0195 (6)
O1	0.0432 (7)	0.0254 (6)	0.0341 (6)	−0.0013 (5)	0.0113 (5)	−0.0091 (5)
O2	0.0514 (8)	0.0321 (7)	0.0377 (7)	0.0001 (6)	0.0138 (6)	−0.0160 (6)
O3	0.0490 (8)	0.0263 (6)	0.0472 (7)	−0.0015 (6)	0.0073 (6)	−0.0204 (6)
O4	0.0455 (8)	0.0274 (6)	0.0448 (7)	−0.0050 (5)	0.0098 (6)	−0.0174 (5)
S1	0.0400 (3)	0.0257 (2)	0.0328 (2)	−0.00173 (17)	0.00760 (18)	−0.01324 (18)

Geometric parameters (Å, º) top

C1—C2	1.486 (3)	C5—N2	1.401 (2)
C1—H1A	0.9700	C6—C7	1.380 (2)
C1—H1B	0.9700	C6—H6	0.9400
C1—H1C	0.9700	C7—N4	1.343 (2)
C2—O1	1.463 (2)	C7—C8	1.466 (2)
C2—H2A	0.9800	C8—O3	1.214 (2)
C2—H2B	0.9800	C8—O4	1.329 (2)
C3—O2	1.214 (2)	C9—O4	1.452 (2)
C3—O1	1.3278 (19)	C9—H9A	0.9700
C3—N1	1.374 (2)	C9—H9B	0.9700
C4—N2	1.338 (2)	C9—H9C	0.9700
C4—N1	1.387 (2)	N1—H1	0.8700
C4—S1	1.6617 (16)	N2—H2	0.8700
C5—N3	1.340 (2)	N3—N4	1.344 (2)
C5—C6	1.397 (2)	N4—H4	0.8700

C2—C1—H1A	109.5	N4—C7—C6	107.60 (14)
C2—C1—H1B	109.5	N4—C7—C8	119.72 (14)
H1A—C1—H1B	109.5	C6—C7—C8	132.67 (16)
C2—C1—H1C	109.5	O3—C8—O4	123.84 (16)
H1A—C1—H1C	109.5	O3—C8—C7	123.32 (16)
H1B—C1—H1C	109.5	O4—C8—C7	112.84 (14)
O1—C2—C1	106.83 (15)	O4—C9—H9A	109.5
O1—C2—H2A	110.4	O4—C9—H9B	109.5
C1—C2—H2A	110.4	H9A—C9—H9B	109.5
O1—C2—H2B	110.4	O4—C9—H9C	109.5
C1—C2—H2B	110.4	H9A—C9—H9C	109.5
H2A—C2—H2B	108.6	H9B—C9—H9C	109.5
O2—C3—O1	125.25 (16)	C3—N1—C4	127.95 (13)
O2—C3—N1	125.62 (15)	C3—N1—H1	116.0
O1—C3—N1	109.13 (13)	C4—N1—H1	116.0
N2—C4—N1	114.69 (14)	C4—N2—C5	129.41 (14)
N2—C4—S1	126.73 (12)	C4—N2—H2	115.3
N1—C4—S1	118.59 (11)	C5—N2—H2	115.3
N3—C5—C6	112.89 (14)	C5—N3—N4	103.49 (14)
N3—C5—N2	114.22 (15)	C7—N4—N3	112.76 (13)
C6—C5—N2	132.89 (15)	C7—N4—H4	123.6
C7—C6—C5	103.26 (14)	N3—N4—H4	123.6
C7—C6—H6	128.4	C3—O1—C2	116.14 (14)
C5—C6—H6	128.4	C8—O4—C9	115.46 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···S1ⁱ	0.87	2.51	3.347 (1)	161
N2—H2···O2	0.87	1.92	2.657 (2)	141
N4—H4···O3ⁱⁱ	0.87	2.03	2.876 (2)	164

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+2, −y−1, −z+1.

Experimental details

Crystal data
Chemical formula	C₉H₁₂N₄O₄S
M_r	272.29
Crystal system, space group	Triclinic, P1
Temperature (K)	208
a, b, c (Å)	8.0855 (8), 9.0035 (8), 9.5959 (9)
α, β, γ (°)	64.510 (1), 82.294 (1), 78.716 (1)
V (Å³)	617.39 (10)
Z	2
Radiation type	Mo Kα
µ (mm⁻¹)	0.28
Crystal size (mm)	0.20 × 0.15 × 0.10

Data collection
Diffractometer	Siemens P4 diffractometer with APEX CCD
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.947, 0.973
No. of measured, independent and observed [I > 2σ(I)] reflections	5852, 2653, 2255
R_int	0.044
(sin θ/λ)_max (Å⁻¹)	0.665

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.040, 0.113, 1.04
No. of reflections	2653
No. of parameters	166
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.39, −0.28

Computer programs: SMART (Bruker, 1997), SAINT (Bruker, 1997), SIR2004 (Burla et al., 2005), SHELXL97 (Sheldrick, 2008), ORTEP-32 (Farrugia, 1997), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···S1ⁱ	0.87	2.51	3.347 (1)	160.6
N2—H2···O2	0.87	1.92	2.657 (2)	141.0
N4—H4···O3ⁱⁱ	0.87	2.03	2.876 (2)	164.2

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+2, −y−1, −z+1.

References

Bruker (1997). SMART and SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2001). SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Burla, M. C., Caliandro, R., Camalli, M., Carrozzini, B., Cascarano, G. L., De Caro, L., Giacovazzo, C., Polidori, G. & Spagna, R. (2005). J. Appl. Cryst. 38, 381–388. Web of Science CrossRef CAS IUCr Journals Google Scholar
Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565. CrossRef IUCr Journals Google Scholar
Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838. CrossRef CAS IUCr Journals Google Scholar
Pask, C. M., Camm, K. D., Kilner, C. A. & Halcrow, M. A. (2006). Tetrahedron Lett. 2531–2534. Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wen, L.-R., Li, M., Zhou, J.-X. & Liu, P. (2006). Acta Cryst. E62, o940–o941. Web of Science CSD CrossRef IUCr Journals Google Scholar

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doi:10.1107/S1600536809016742

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