tert-Butyl 4-(1-methyl-1H-pyrazol-5-yl)piperidine-1-carboxyl­ate

Richter, D.; Kath, J.C.; Rheingold, A.L.; DiPasquale, A.; Yanovsky, A.

doi:10.1107/S1600536809010332

organic compounds

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Volume 65| Part 4| April 2009| Page o870

doi:10.1107/S1600536809010332

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tert-Butyl 4-(1-methyl-1H-pyrazol-5-yl)piperidine-1-carboxylate

Daniel Richter,^a John C. Kath,^a Arnold L. Rheingold,^b Antonio DiPasquale ^b and Alex Yanovsky ^a ^*

^aPfizer Global Research and Development, La Jolla Labs, 10614 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 15 March 2009; accepted 20 March 2009; online 25 March 2009)

The reaction of (E)-tert-butyl 4-[3-(dimethylamino)acryloyl]piperidine-1-carboxylate with methylhydrazine leads to the formation of the title compound, C₁₄H₂₃N₃O₂, with a 1-methyl-1H-pyrazol-5-yl substituent. The plane of the pyrazole ring forms a dihedral angle of 33.4 (1)° with the approximate mirror plane of the piperidine ring.

Related literature

For the structure of a related compound with a five-membered aromatic ring bonded to a saturated six-membered ring, see: Basil et al. (2002 ).

Experimental

Crystal data

C₁₄H₂₃N₃O₂
M_r = 265.35
Monoclinic, P 2₁ /c
a = 11.356 (3) Å
b = 11.735 (3) Å
c = 11.245 (2) Å
β = 100.224 (3)°
V = 1474.8 (6) Å³
Z = 4
Mo Kα radiation
μ = 0.08 mm⁻¹
T = 198 K
0.12 × 0.12 × 0.06 mm

Data collection

Siemens P4 APEX CCD area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2001 ) T_min = 0.990, T_max = 0.995
14589 measured reflections
3253 independent reflections
2157 reflections with I > 2σ(I)
R_int = 0.063

Refinement

R[F² > 2σ(F²)] = 0.055
wR(F²) = 0.162
S = 1.03
3253 reflections
176 parameters
H-atom parameters constrained
Δρ_max = 0.28 e Å⁻³
Δρ_min = −0.17 e Å⁻³

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/S1600536809010332/rz2303sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536809010332/rz2303Isup2.hkl

checkCIF report

Comment top

The reaction of (E)-tert-butyl 4-(3-(dimethylamino)acryloyl)piperidine-1-carboxylate with methylhydrazine leads to the formation of a pyrazole ring and can potentially produce two compounds differing in the location of the methyl group. The present X-ray study unambiguously established the structure of the product of the above cyclization as the piperidine derivative with 1-methylpyrazol-5-yl substituent (Fig.1).

The mean plane of the pyrazolyl ring forms a dihedral angle of 33.4 (1)° with the plane drawn through the C6, C3, N1, C10 atoms; this plane in fact coincides with the approximate mirror plane of the piperidine ring. The known structures featuring direct bonding between an aromatic 5-membered ring and a cycloxane/piperidine ring are surprisingly scarce. The conformation of the title compound is substantially different from that of (1R,2R,3S)-1-((4S)-4-tert-butyl-2-oxazolinyl)-2-phenyl-3-(phenylsulfonyl)cyclohexane (Basil et al., 2002), where the 5-membered ring carries neither H atoms nor any other substituents in 1 and 3 positions and is effectively coplanar with the mirror plane of the cyclohexyl group.

Related literature top

For the structure of a related compound with a five-membered aromatic ring bonded to a saturated six-membered ring, see: Basil et al. (2002).

Experimental top

A mixture of (E)-tert-butyl 4-(3-(dimethylamino)acryloyl)piperidine-1-carboxylate (3.95 g, 14 mmol) and methylhydrazine (0.77 ml, 1.05 eq) was refluxed for 2 h in ethanol (20 ml). The reaction mixture was then cooled down and evaporated to dryness. The residue was dissolved in 2-methyltetrahydrofurane, and the crystals formed were filtered to give 1.05 g (32%) of a white solid. It was then again recrystallized by slow evaporation of an ethylactetate solution to obtain the crystals suitable for X-ray study. ¹H NMR (400 MHz, DMSO-d6) d, p.p.m.: 1.41 (s, 11H), 1.81 (m, 2H), 2.85 (m, 3H), 3.76 (s, 3H), 4.02 (m, 2 H), 6.05 (d, J = 2.01 Hz, 1H) 7.27 (d, J = 1.76 Hz, 1H).

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. The 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.

tert-Butyl 4-(1-methyl-1H-pyrazol-5-yl)piperidine-1-carboxylate top

Crystal data top

C₁₄H₂₃N₃O₂	F(000) = 576
M_r = 265.35	D_x = 1.195 Mg m⁻³
Monoclinic, P2₁/c	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybc	Cell parameters from 4631 reflections
a = 11.356 (3) Å	θ = 2.5–26.9°
b = 11.735 (3) Å	µ = 0.08 mm⁻¹
c = 11.245 (2) Å	T = 198 K
β = 100.224 (3)°	Block, colorless
V = 1474.8 (6) Å³	0.12 × 0.12 × 0.06 mm
Z = 4

Data collection top

Siemens P4 APEX CCD area-detector diffractometer	3253 independent reflections
Radiation source: fine-focus sealed tube	2157 reflections with I > 2σ(I)
Graphite monochromator	R_int = 0.063
ϕ and ω scans	θ_max = 28.2°, θ_min = 1.8°
Absorption correction: multi-scan (SADABS; Bruker, 2001)	h = −14→15
T_min = 0.990, T_max = 0.995	k = −15→15
14589 measured reflections	l = −13→5

Refinement top

Refinement on F²	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F² > 2σ(F²)] = 0.055	Hydrogen site location: inferred from neighbouring sites
wR(F²) = 0.162	H-atom parameters constrained
S = 1.03	w = 1/[σ²(F_o²) + (0.0866P)² + 0.0739P] where P = (F_o² + 2F_c²)/3
3253 reflections	(Δ/σ)_max = 0.001
176 parameters	Δρ_max = 0.28 e Å⁻³
0 restraints	Δρ_min = −0.17 e Å⁻³

Crystal data top

C₁₄H₂₃N₃O₂	V = 1474.8 (6) Å³
M_r = 265.35	Z = 4
Monoclinic, P2₁/c	Mo Kα radiation
a = 11.356 (3) Å	µ = 0.08 mm⁻¹
b = 11.735 (3) Å	T = 198 K
c = 11.245 (2) Å	0.12 × 0.12 × 0.06 mm
β = 100.224 (3)°

Data collection top

Siemens P4 APEX CCD area-detector diffractometer	3253 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2001)	2157 reflections with I > 2σ(I)
T_min = 0.990, T_max = 0.995	R_int = 0.063
14589 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.055	0 restraints
wR(F²) = 0.162	H-atom parameters constrained
S = 1.03	Δρ_max = 0.28 e Å⁻³
3253 reflections	Δρ_min = −0.17 e Å⁻³
176 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	0.47096 (16)	0.26958 (14)	0.23649 (18)	0.0443 (5)
H1A	0.5242	0.3157	0.2974	0.053*
H1B	0.3968	0.3136	0.2091	0.053*
C2	0.53249 (16)	0.24635 (14)	0.12987 (18)	0.0446 (4)
H2A	0.5568	0.3196	0.0978	0.054*
H2B	0.4754	0.2087	0.0650	0.054*
C3	0.64312 (15)	0.17030 (14)	0.16493 (17)	0.0415 (4)
H3	0.7022	0.2119	0.2262	0.050*
C4	0.60673 (17)	0.06158 (14)	0.22336 (18)	0.0460 (5)
H4A	0.5525	0.0165	0.1623	0.055*
H4B	0.6789	0.0150	0.2521	0.055*
C5	0.54446 (17)	0.08740 (16)	0.32860 (19)	0.0510 (5)
H5A	0.5171	0.0154	0.3606	0.061*
H5B	0.6016	0.1243	0.3940	0.061*
C6	0.70107 (14)	0.14487 (14)	0.05859 (17)	0.0420 (4)
C7	0.68977 (17)	0.05354 (15)	−0.01942 (18)	0.0480 (5)
H7	0.6425	−0.0129	−0.0166	0.058*
C8	0.76220 (19)	0.07921 (17)	−0.10319 (19)	0.0558 (5)
H8	0.7718	0.0307	−0.1684	0.067*
C9	0.82255 (17)	0.32615 (16)	0.0698 (2)	0.0564 (5)
H9A	0.8848	0.3545	0.0272	0.085*
H9B	0.8564	0.3156	0.1555	0.085*
H9C	0.7569	0.3814	0.0618	0.085*
C10	0.34339 (16)	0.14793 (15)	0.34221 (18)	0.0454 (5)
C11	0.15104 (16)	0.23821 (15)	0.35928 (18)	0.0463 (5)
C12	0.07212 (18)	0.14266 (17)	0.2992 (2)	0.0583 (5)
H12A	0.0699	0.1451	0.2117	0.088*
H12B	−0.0091	0.1520	0.3160	0.088*
H12C	0.1046	0.0692	0.3310	0.088*
C13	0.16876 (19)	0.2322 (2)	0.4953 (2)	0.0613 (6)
H13A	0.1967	0.1559	0.5222	0.092*
H13B	0.0927	0.2480	0.5218	0.092*
H13C	0.2284	0.2889	0.5302	0.092*
C14	0.10122 (16)	0.35355 (16)	0.3152 (2)	0.0525 (5)
H14A	0.1540	0.4138	0.3546	0.079*
H14B	0.0212	0.3630	0.3351	0.079*
H14C	0.0962	0.3585	0.2275	0.079*
N1	0.44168 (12)	0.16258 (11)	0.29133 (15)	0.0440 (4)
N2	0.77748 (13)	0.21780 (12)	0.01773 (15)	0.0458 (4)
N3	0.81639 (14)	0.17886 (14)	−0.08198 (16)	0.0543 (5)
O1	0.32504 (12)	0.06460 (12)	0.40018 (13)	0.0588 (4)
O2	0.26749 (11)	0.23697 (10)	0.31802 (12)	0.0475 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0469 (10)	0.0301 (9)	0.0581 (13)	−0.0007 (7)	0.0151 (8)	0.0013 (8)
C2	0.0499 (10)	0.0311 (8)	0.0540 (12)	0.0023 (7)	0.0127 (8)	0.0036 (8)
C3	0.0438 (9)	0.0338 (8)	0.0470 (12)	−0.0004 (7)	0.0082 (8)	−0.0029 (8)
C4	0.0483 (10)	0.0358 (9)	0.0546 (12)	0.0050 (7)	0.0110 (8)	0.0044 (8)
C5	0.0524 (11)	0.0447 (10)	0.0575 (13)	0.0096 (8)	0.0141 (9)	0.0113 (9)
C6	0.0416 (9)	0.0358 (9)	0.0478 (12)	0.0056 (7)	0.0060 (8)	0.0026 (8)
C7	0.0569 (11)	0.0353 (9)	0.0513 (12)	0.0047 (8)	0.0081 (9)	−0.0043 (8)
C8	0.0687 (13)	0.0481 (11)	0.0515 (13)	0.0151 (10)	0.0131 (10)	−0.0046 (9)
C9	0.0516 (11)	0.0455 (11)	0.0737 (15)	−0.0084 (8)	0.0151 (10)	−0.0055 (10)
C10	0.0502 (10)	0.0382 (10)	0.0478 (12)	−0.0027 (8)	0.0089 (8)	−0.0008 (8)
C11	0.0439 (10)	0.0493 (11)	0.0483 (12)	−0.0036 (8)	0.0150 (8)	−0.0024 (8)
C12	0.0547 (11)	0.0539 (12)	0.0677 (15)	−0.0089 (9)	0.0144 (10)	−0.0050 (10)
C13	0.0612 (13)	0.0716 (15)	0.0534 (14)	−0.0026 (10)	0.0167 (10)	−0.0002 (11)
C14	0.0455 (10)	0.0532 (12)	0.0595 (14)	0.0012 (8)	0.0117 (9)	−0.0057 (9)
N1	0.0465 (8)	0.0341 (7)	0.0533 (10)	0.0032 (6)	0.0141 (7)	0.0047 (7)
N2	0.0480 (8)	0.0383 (8)	0.0530 (10)	0.0031 (6)	0.0145 (7)	−0.0004 (7)
N3	0.0592 (10)	0.0511 (10)	0.0565 (12)	0.0107 (8)	0.0208 (8)	0.0020 (8)
O1	0.0623 (9)	0.0479 (8)	0.0700 (11)	−0.0008 (6)	0.0220 (7)	0.0149 (7)
O2	0.0457 (7)	0.0441 (7)	0.0558 (9)	0.0029 (5)	0.0174 (6)	0.0066 (6)

Geometric parameters (Å, º) top

C1—N1	1.463 (2)	C9—N2	1.454 (2)
C1—C2	1.516 (3)	C9—H9A	0.9800
C1—H1A	0.9900	C9—H9B	0.9800
C1—H1B	0.9900	C9—H9C	0.9800
C2—C3	1.534 (2)	C10—O1	1.214 (2)
C2—H2A	0.9900	C10—O2	1.351 (2)
C2—H2B	0.9900	C10—N1	1.353 (2)
C3—C6	1.494 (3)	C11—O2	1.477 (2)
C3—C4	1.525 (2)	C11—C13	1.508 (3)
C3—H3	1.0000	C11—C14	1.516 (3)
C4—C5	1.513 (3)	C11—C12	1.517 (3)
C4—H4A	0.9900	C12—H12A	0.9800
C4—H4B	0.9900	C12—H12B	0.9800
C5—N1	1.464 (2)	C12—H12C	0.9800
C5—H5A	0.9900	C13—H13A	0.9800
C5—H5B	0.9900	C13—H13B	0.9800
C6—N2	1.356 (2)	C13—H13C	0.9800
C6—C7	1.377 (2)	C14—H14A	0.9800
C7—C8	1.389 (3)	C14—H14B	0.9800
C7—H7	0.9500	C14—H14C	0.9800
C8—N3	1.323 (3)	N2—N3	1.355 (2)
C8—H8	0.9500

N1—C1—C2	110.50 (14)	N2—C9—H9B	109.5
N1—C1—H1A	109.6	H9A—C9—H9B	109.5
C2—C1—H1A	109.6	N2—C9—H9C	109.5
N1—C1—H1B	109.6	H9A—C9—H9C	109.5
C2—C1—H1B	109.6	H9B—C9—H9C	109.5
H1A—C1—H1B	108.1	O1—C10—O2	124.54 (17)
C1—C2—C3	111.88 (15)	O1—C10—N1	124.25 (17)
C1—C2—H2A	109.2	O2—C10—N1	111.19 (15)
C3—C2—H2A	109.2	O2—C11—C13	110.63 (16)
C1—C2—H2B	109.2	O2—C11—C14	102.07 (14)
C3—C2—H2B	109.2	C13—C11—C14	110.36 (16)
H2A—C2—H2B	107.9	O2—C11—C12	110.10 (15)
C6—C3—C4	111.67 (14)	C13—C11—C12	112.29 (17)
C6—C3—C2	111.56 (15)	C14—C11—C12	110.95 (17)
C4—C3—C2	108.97 (14)	C11—C12—H12A	109.5
C6—C3—H3	108.2	C11—C12—H12B	109.5
C4—C3—H3	108.2	H12A—C12—H12B	109.5
C2—C3—H3	108.2	C11—C12—H12C	109.5
C5—C4—C3	111.68 (14)	H12A—C12—H12C	109.5
C5—C4—H4A	109.3	H12B—C12—H12C	109.5
C3—C4—H4A	109.3	C11—C13—H13A	109.5
C5—C4—H4B	109.3	C11—C13—H13B	109.5
C3—C4—H4B	109.3	H13A—C13—H13B	109.5
H4A—C4—H4B	107.9	C11—C13—H13C	109.5
N1—C5—C4	110.87 (15)	H13A—C13—H13C	109.5
N1—C5—H5A	109.5	H13B—C13—H13C	109.5
C4—C5—H5A	109.5	C11—C14—H14A	109.5
N1—C5—H5B	109.5	C11—C14—H14B	109.5
C4—C5—H5B	109.5	H14A—C14—H14B	109.5
H5A—C5—H5B	108.1	C11—C14—H14C	109.5
N2—C6—C7	105.57 (17)	H14A—C14—H14C	109.5
N2—C6—C3	122.99 (15)	H14B—C14—H14C	109.5
C7—C6—C3	131.39 (16)	C10—N1—C1	123.62 (14)
C6—C7—C8	105.30 (17)	C10—N1—C5	118.57 (15)
C6—C7—H7	127.4	C1—N1—C5	114.12 (14)
C8—C7—H7	127.4	N3—N2—C6	112.94 (15)
N3—C8—C7	112.44 (17)	N3—N2—C9	118.98 (15)
N3—C8—H8	123.8	C6—N2—C9	128.05 (17)
C7—C8—H8	123.8	C8—N3—N2	103.74 (15)
N2—C9—H9A	109.5	C10—O2—C11	121.27 (13)

Experimental details

Crystal data
Chemical formula	C₁₄H₂₃N₃O₂
M_r	265.35
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	198
a, b, c (Å)	11.356 (3), 11.735 (3), 11.245 (2)
β (°)	100.224 (3)
V (Å³)	1474.8 (6)
Z	4
Radiation type	Mo Kα
µ (mm⁻¹)	0.08
Crystal size (mm)	0.12 × 0.12 × 0.06

Data collection
Diffractometer	Siemens P4 APEX CCD area-detector diffractometer
Absorption correction	Multi-scan (SADABS; Bruker, 2001)
T_min, T_max	0.990, 0.995
No. of measured, independent and observed [I > 2σ(I)] reflections	14589, 3253, 2157
R_int	0.063
(sin θ/λ)_max (Å⁻¹)	0.665

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.055, 0.162, 1.03
No. of reflections	3253
No. of parameters	176
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.17

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

References

Basil, L. F., Meyers, A. I. & Hassner, A. (2002). Tetrahedron, 58, 207–213. Web of Science CSD CrossRef CAS Google Scholar
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
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar