3-Bromo-7-methoxy-2-(tetra­hydro­pyran-2-yl)­pyrazolo­[4,3-d]­pyrimidine

In the title compound, C₁₁H₁₃BrN₄O₂, the pyrimidine and pyrazole rings make a dihedral angle of 3.8 (6)°. The pendant tetra­hydro­pyran ring is in a chair conformation and its mean plane makes an interplanar angle of 52.5 (6)° with the pyrazole ring. There is a short Br...O intermolecular contact of 2.994 (7) Å.

Key indicators

• Single-crystal X-ray study
• T = 163 K
• Mean [sigma](C-C) = 0.015 Å
• R factor = 0.059
• wR factor = 0.147
• Data-to-parameter ratio = 12.6

checkCIF results

No syntax errors found

ADDSYM reports no extra symmetry


 Alert Level C:



PLAT_163  Alert C Missing or Zero su (esd) on z-coordinate for .       BR1

PLAT_213  Alert C Atom O1      has ADP max/min Ratio ...........       3.40 prolate

General Notes



REFLT_03
         From the CIF: _diffrn_reflns_theta_max           26.06
         From the CIF: _reflns_number_total               1475
         From the CIF: _diffrn_reflns_limit_ max hkl   12.   21.    6.
         From the CIF: _diffrn_reflns_limit_ min hkl  -12.  -14.   -7.
         TEST1: Expected hkl limits for theta max
         Calculated maximum hkl   15.   21.    7.
         Calculated minimum hkl  -15.  -21.   -7.
          ALERT: Expected hkl max differ from CIF values

REFLT_03
         From the CIF: _diffrn_reflns_theta_max           26.06
         From the CIF: _reflns_number_total               1475
         Count of symmetry unique reflns         1314
         Completeness (_total/calc)            112.25%
         TEST3: Check Friedels for noncentro structure
         Estimate of Friedel pairs measured       161
         Fraction of Friedel pairs measured     0.123
         Are heavy atom types Z>Si present          yes
          WARNING: Large fraction of Friedel related reflns may
                   be needed to determine absolute structure


 0 Alert Level A = Potentially serious problem

 0 Alert Level B = Potential problem

 2 Alert Level C = Please check

---

S1. Comment

The title compound, (I), was studied in order to confirm the regioselectivity, based on ¹³C NMR, of the critical tetrahydropyranyl-protecting group. The crystal structure is built of isolated molecules (Fig. 1) and only weak intermolecular contacts e.g. C5—H5···O2ⁱ [symmetry code: (i) x − 1/2, 3/2 − y, z] with C5···O2ⁱ = 3.29 (1) Å. There is also a short intermolecular contact between Br1 and O1ⁱⁱ of 2.994 (7) Å [symmetry code: (ii) −x, 1 − y, z − 1/2]. A search of the Cambridge Structural Database (Allen & Kennard, 1993; CCDC, 2002a) gives the (closest) similar interaction of 3.024 Å in 5-bromo-11-ethylenedioxy-5-nitro-2- oxapentacyclo[7.3.0^3,7.O^4,12O^6,11]dodecane (Watson et al., 1990) and, interestingly, this is the only interaction between the molecules in one direction in the lattice (CCDC, 2002b). Two other short Br···O intermolecular distances have been reported, viz. 3.094 (Gu et al., 1986) and 3.102 Å (Tomilov et al., 1999), but in these latter cases there are further intermolecular contacts between the same molecules. There is also one close intramolecular interaction here, viz. C1'-H1'···Br1 with C1'···Br1 = 3.27 (1) Å.

The C—Br distance is 1.85 (1) Å, identical to that in 4-bromo-3-(3-pyridyl)sydnone (Hasek et al., 1979); C—Br bond distances from sp²-hybridized C atoms vary in the range 1.793–1.932 Å (CCDC, 2002a). The fused five- and six-membered rings are each planar, with average deviations of 0.008 (6) and 0.007 (7) Å, respectively; their least-squares planes form a dihedral angle of 3.8 (6)°. The pendant tetrahydropyran ring (O1/C1'–C5') is in a chair conformation [Q = 0.57 (1) Å and θ 3.4 (12)°; Boeyens, 1978] and the mean plane through this ring makes an angle of 52.5 (6) Å to the pyrazole ring.

S2. Experimental

The title compound was prepared as described by Stone et al. (1979) and recrystallized from methanol.

S3. Refinement

The _measured_fraction_theta_max was low (0.76), which follows a collection algorithm limit error on the h index. The data-to-parameter ratio and Flack (1983) parameter s.u. are adequate, though it was not possible to refine all non-H atoms with anisotropic displacement parameters. All H atoms were included in the riding-model approximation with an isotropic displacement parameter constrained to 1.2 times that of the equivalent U_eq value of their parent atom (SHELXL97; Sheldrick, 1997).

Computing details

Data collection: SMART (Siemens, 1996); cell refinement: SMART (Siemens, 1996); data reduction: SAINT (Siemens, 1996) and SADABS (Sheldrick, 1996); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. The molecular structure of (I) (Farrugia, 1997). Displacement ellipsoids are drawn at the 50% probability level.

(I)

Crystal data

C11H13BrN4O2	F(000) = 632
Mr = 313.16	Dx = 1.723 Mg m^−3
Orthorhombic, Pna21	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2c -2n	Cell parameters from 2337 reflections
a = 12.4224 (4) Å	θ = 2.9–25.8°
b = 17.1489 (5) Å	µ = 3.41 mm^−1
c = 5.6680 (1) Å	T = 163 K
V = 1207.46 (6) Å^3	Needle, pale yellow
Z = 4	0.50 × 0.06 × 0.04 mm

Data collection

Bruker P4 diffractometer	1475 independent reflections
Radiation source: fine-focus sealed tube	1188 reflections with I > 2σ(I)
Graphite monochromator	Rint = 0.058
Detector resolution: 8.192 pixels mm^-1	θmax = 26.1°, θmin = 2.9°
ω scans	h = −12→12
Absorption correction: multi-scan (Blessing, 1995)	k = −14→21
Tmin = 0.290, Tmax = 0.876	l = −7→6
3279 measured reflections

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: constr
R[F^2 > 2σ(F^2)] = 0.059	H-atom parameters constrained
wR(F^2) = 0.147	w = 1/[σ^2(Fo^2) + (0.0903P)^2] where P = (Fo^2 + 2Fc^2)/3
S = 0.99	(Δ/σ)max = 0.001
1475 reflections	Δρmax = 1.00 e Å^−3
117 parameters	Δρmin = −1.45 e Å^−3
0 restraints	Absolute structure: (Flack, 1983), 161 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: 0.00 (3)

Special details

Experimental. Crystal decay was monitored by repeating the initial 10 frames at the end of the data collection (shell) and analyzing duplicate reflections. The standard 0.8 mm diameter collimator was used.

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 (Ų)

	x	y	z	Uiso*/Ueq
Br1	−0.03565 (7)	0.58048 (5)	0.18411	0.0222 (3)
O1	0.2046 (6)	0.4822 (4)	0.3585 (11)	0.0215 (16)
O2	0.1935 (6)	0.7450 (4)	1.0545 (11)	0.0248 (18)
N1	0.1944 (7)	0.6425 (4)	0.6482 (13)	0.022 (2)*
N2	0.1527 (7)	0.6059 (5)	0.4598 (14)	0.020 (2)
N4	−0.0742 (8)	0.7174 (5)	0.6385 (12)	0.022 (2)*
N6	0.0188 (8)	0.7792 (5)	0.9593 (13)	0.026 (2)*
C3	0.0452 (10)	0.6238 (6)	0.4249 (17)	0.024 (2)*
C3A	0.0185 (10)	0.6757 (6)	0.5928 (17)	0.019 (3)
C5	−0.0675 (10)	0.7644 (6)	0.8066 (16)	0.031 (3)*
H5	−0.1303	0.7946	0.8349	0.037*
C7	0.1070 (9)	0.7388 (6)	0.9201 (14)	0.020 (2)*
C7A	0.1108 (9)	0.6856 (5)	0.7316 (14)	0.018 (3)
C8	0.1908 (10)	0.8025 (7)	1.2440 (15)	0.028 (3)
H8A	0.2064	0.8543	1.1795	0.033*
H8B	0.2450	0.7891	1.3630	0.033*
H8C	0.1193	0.8027	1.3169	0.033*
C1'	0.2200 (10)	0.5608 (6)	0.3048 (16)	0.025 (2)*
H1'	0.1952	0.5698	0.1391	0.030*
C2'	0.3360 (10)	0.5844 (6)	0.3212 (17)	0.030 (2)*
H2'A	0.3628	0.5767	0.4841	0.036*
H2'B	0.3441	0.6402	0.2798	0.036*
C3'	0.4003 (10)	0.5337 (6)	0.1486 (19)	0.034 (3)*
H3'A	0.3809	0.5477	−0.0155	0.041*
H3'B	0.4782	0.5434	0.1698	0.041*
C4'	0.3763 (8)	0.4479 (5)	0.191 (3)	0.029 (2)
H4'A	0.4101	0.4162	0.0654	0.035*
H4'B	0.4073	0.4317	0.3442	0.035*
C5'	0.2571 (9)	0.4340 (5)	0.192 (3)	0.031 (2)
H5'A	0.2277	0.4444	0.0330	0.037*
H5'B	0.2428	0.3786	0.2309	0.037*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
Br1	0.0131 (6)	0.0235 (5)	0.0299 (4)	−0.0043 (5)	−0.0018 (6)	−0.0031 (6)
O1	0.006 (5)	0.013 (3)	0.045 (4)	−0.003 (4)	0.008 (3)	−0.006 (3)
O2	0.014 (5)	0.028 (4)	0.032 (3)	−0.002 (4)	−0.004 (3)	0.000 (3)
N2	0.012 (6)	0.015 (4)	0.033 (4)	0.006 (5)	0.003 (3)	−0.002 (3)
C3A	0.006 (8)	0.020 (5)	0.031 (4)	−0.006 (6)	0.001 (4)	0.004 (4)
C7A	0.012 (8)	0.014 (5)	0.028 (5)	−0.005 (6)	−0.001 (3)	−0.001 (3)
C8	0.008 (8)	0.036 (7)	0.039 (6)	−0.006 (7)	0.000 (4)	−0.009 (4)
C4'	0.011 (7)	0.026 (5)	0.051 (5)	0.008 (5)	−0.001 (7)	0.000 (7)
C5'	0.020 (8)	0.023 (5)	0.050 (5)	0.001 (5)	−0.003 (8)	0.004 (7)

Geometric parameters (Å, º)

Br1—C3	1.850 (10)	C8—H8A	0.9800
O1—C1'	1.394 (12)	C8—H8B	0.9800
O1—C5'	1.413 (15)	C8—H8C	0.9800
O2—C7	1.322 (12)	C1'—C2'	1.500 (17)
O2—C8	1.458 (11)	C1'—H1'	1.0000
N1—N2	1.343 (11)	C2'—C3'	1.534 (15)
N1—C7A	1.360 (12)	C2'—H2'A	0.9900
N2—C3	1.384 (14)	C2'—H2'B	0.9900
N2—C1'	1.439 (13)	C3'—C4'	1.519 (14)
N4—C5	1.251 (12)	C3'—H3'A	0.9900
N4—C3A	1.380 (14)	C3'—H3'B	0.9900
N6—C7	1.315 (14)	C4'—C5'	1.500 (15)
N6—C5	1.401 (14)	C4'—H4'A	0.9900
C3—C3A	1.344 (15)	C4'—H4'B	0.9900
C3A—C7A	1.401 (14)	C5'—H5'A	0.9900
C5—H5	0.9500	C5'—H5'B	0.9900
C7—C7A	1.406 (13)
C1'—O1—C5'	110.9 (8)	O1—C1'—C2'	112.3 (9)
C7—O2—C8	117.4 (8)	N2—C1'—C2'	112.0 (8)
N2—N1—C7A	103.6 (8)	O1—C1'—H1'	108.2
N1—N2—C3	112.5 (8)	N2—C1'—H1'	108.2
N1—N2—C1'	120.9 (9)	C2'—C1'—H1'	108.2
C3—N2—C1'	126.3 (9)	C1'—C2'—C3'	107.9 (9)
C5—N4—C3A	115.0 (10)	C1'—C2'—H2'A	110.1
C7—N6—C5	116.0 (9)	C3'—C2'—H2'A	110.1
C3A—C3—N2	106.5 (10)	C1'—C2'—H2'B	110.1
C3A—C3—Br1	130.8 (10)	C3'—C2'—H2'B	110.1
N2—C3—Br1	122.7 (8)	H2'A—C2'—H2'B	108.4
C3—C3A—N4	133.0 (10)	C4'—C3'—C2'	110.3 (10)
C3—C3A—C7A	106.0 (10)	C4'—C3'—H3'A	109.6
N4—C3A—C7A	120.9 (9)	C2'—C3'—H3'A	109.6
N4—C5—N6	129.6 (12)	C4'—C3'—H3'B	109.6
N4—C5—H5	115.2	C2'—C3'—H3'B	109.6
N6—C5—H5	115.2	H3'A—C3'—H3'B	108.1
N6—C7—O2	122.5 (8)	C5'—C4'—C3'	110.4 (9)
N6—C7—C7A	119.9 (10)	C5'—C4'—H4'A	109.6
O2—C7—C7A	117.6 (10)	C3'—C4'—H4'A	109.6
N1—C7A—C3A	111.3 (8)	C5'—C4'—H4'B	109.6
N1—C7A—C7	130.0 (10)	C3'—C4'—H4'B	109.6
C3A—C7A—C7	118.6 (10)	H4'A—C4'—H4'B	108.1
O2—C8—H8A	109.5	O1—C5'—C4'	111.4 (11)
O2—C8—H8B	109.5	O1—C5'—H5'A	109.3
H8A—C8—H8B	109.5	C4'—C5'—H5'A	109.3
O2—C8—H8C	109.5	O1—C5'—H5'B	109.3
H8A—C8—H8C	109.5	C4'—C5'—H5'B	109.3
H8B—C8—H8C	109.5	H5'A—C5'—H5'B	108.0
O1—C1'—N2	107.9 (8)
C7A—N1—N2—C3	−1.0 (10)	C3—C3A—C7A—N1	1.6 (11)
C7A—N1—N2—C1'	172.8 (8)	N4—C3A—C7A—N1	−176.4 (8)
N1—N2—C3—C3A	2.0 (12)	C3—C3A—C7A—C7	178.5 (9)
C1'—N2—C3—C3A	−171.4 (9)	N4—C3A—C7A—C7	0.4 (14)
N1—N2—C3—Br1	−178.3 (6)	N6—C7—C7A—N1	174.6 (9)
C1'—N2—C3—Br1	8.2 (14)	O2—C7—C7A—N1	−6.5 (15)
N2—C3—C3A—N4	175.6 (10)	N6—C7—C7A—C3A	−1.6 (14)
Br1—C3—C3A—N4	−3.9 (18)	O2—C7—C7A—C3A	177.3 (8)
N2—C3—C3A—C7A	−2.1 (11)	C5'—O1—C1'—N2	172.1 (9)
Br1—C3—C3A—C7A	178.3 (8)	C5'—O1—C1'—C2'	−64.0 (10)
C5—N4—C3A—C3	−176.2 (11)	N1—N2—C1'—O1	102.2 (10)
C5—N4—C3A—C7A	1.3 (13)	C3—N2—C1'—O1	−84.8 (12)
C3A—N4—C5—N6	−2.2 (15)	N1—N2—C1'—C2'	−21.8 (12)
C7—N6—C5—N4	1.1 (15)	C3—N2—C1'—C2'	151.1 (10)
C5—N6—C7—O2	−177.9 (8)	O1—C1'—C2'—C3'	59.0 (10)
C5—N6—C7—C7A	1.0 (13)	N2—C1'—C2'—C3'	−179.5 (8)
C8—O2—C7—N6	−3.5 (13)	C1'—C2'—C3'—C4'	−52.3 (12)
C8—O2—C7—C7A	177.6 (8)	C2'—C3'—C4'—C5'	51.5 (16)
N2—N1—C7A—C3A	−0.4 (10)	C1'—O1—C5'—C4'	61.1 (13)
N2—N1—C7A—C7	−176.8 (9)	C3'—C4'—C5'—O1	−55.2 (16)