6-Amino-3-(β-D-2-de­oxy-erythro-furanos­yl)-2-fluoro­pyridine: a nucleoside analogue

The title compound [systematic name: (2R,3R,5R)-5-(6-amino-2-fluoro­pyridin-3-yl)-2-(hydroxy­meth­yl)-2,3,4,5-tetra­hydro­furan-3-ol], C₁₀H₁₃FN₂O₃, is a C-nucleoside with fluorine replacing the O2 carbonyl of deoxy­cytidine (dC). The furan­ose ring adopts a C2′-endo conformation, while the orientation of the pyridine ring with respect to the sugar group is anti. The C-glycosidic bond torsion angle χ is anti [−121.32 (13)°]. The C—C glycosidic bond is 1.4952 (17) Å in length, while the C—F bond length is 1.3463 (16) Å.

Key indicators

• Single-crystal X-ray study
• T = 193 K
• Mean [sigma](C-C) = 0.002 Å
• R factor = 0.033
• wR factor = 0.082
• Data-to-parameter ratio = 10.0

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT720_ALERT_4_C Number of Unusual/Non-Standard Label(s) ........          4

Alert level G
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           28.40
           From the CIF: _reflns_number_total               1469
           Count of symmetry unique reflns         1477
           Completeness (_total/calc)             99.46%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         0
           Fraction of Friedel pairs measured     0.000
           Are heavy atom types Z>Si present         no

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
   1 ALERT level C = Check and explain
   1 ALERT level G = General alerts; check

   0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   0 ALERT type 2 Indicator that the structure model may be wrong or deficient
   0 ALERT type 3 Indicator that the structure quality may be low
   2 ALERT type 4 Improvement, methodology, query or suggestion

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Computing details

Data collection: SMART (Bruker, 2001); cell refinement: SAINT (Bruker, 2001); data reduction: SAINT; program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: SHELXTL (Bruker, 1998); software used to prepare material for publication: SHELXTL.

(2R,3R,5R)-5-(6-amino-2-fluoropyridin-3-yl)-2-(hydroxymethyl)-2,3,4,5- tetrahydrofuran-3-ol

Crystal data

C10H13FN2O3	Dx = 1.515 Mg m^−3
Mr = 228.22	Melting point: 425 K
Orthorhombic, P212121	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: P 2ac 2ab	Cell parameters from 3580 reflections
a = 6.3295 (16) Å	θ = 2.3–28.4°
b = 11.365 (3) Å	µ = 0.12 mm^−1
c = 13.908 (3) Å	T = 193 K
V = 1000.5 (4) Å^3	Chunk, colourless
Z = 4	0.2 × 0.1 × 0.1 mm
F(000) = 480

Data collection

Bruker SMART CCD area-detector diffractometer	1365 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.042
Graphite monochromator	θmax = 28.4°
φ and ω scans	h = −6→8
7552 measured reflections	k = −13→15
1469 independent reflections	l = −18→12

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.033	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.082	H-atom parameters constrained
S = 1.13	w = 1/[σ^2(Fo^2) + (0.0513P)^2] where P = (Fo^2 + 2Fc^2)/3
1469 reflections	(Δ/σ)max = 0.001
147 parameters	Δρmax = 0.32 e Å^−3
0 restraints	Δρmin = −0.14 e Å^−3

Special details

Experimental. Data was collected using a BRUKER SMART CCD (charge coupled device) based diffractometer equipped with an oxford low-temperature apparatus perating at 193 K. A suitable crystal was chosen and mounted on a glass fiber using grease. Data were measured using omega scans of 0.3° per frame for 45 s, such that a hemisphere was collected. A total of 1271 frames were collected with a final resolution of 0.84 Å. The first 50 frames were recollected at the end of data collection to monitor for decay. Cell parameters were retrieved using SMART software and refined using SAINT on all observed reflections. Data reduction was performed using the SAINT software which corrects for Lp and decay. Absorption corrections were applied using SADABS based on Blessing,(1995). The structures are solved by the direct method using the SHELX90 program and refined by least squares method on F2 SHELXL93, incorporated in SHELXTL V6.1.

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
O5'	0.94272 (16)	0.54968 (8)	0.46098 (7)	0.0274 (2)
H5B	1.0474	0.5160	0.4859	0.041*
O4'	0.78603 (15)	0.32345 (8)	0.52483 (6)	0.0221 (2)
O3'	0.30307 (14)	0.42131 (8)	0.50010 (7)	0.0287 (2)
H3	0.3072	0.3474	0.5006	0.043*
F1	0.64826 (17)	0.15831 (9)	0.75953 (7)	0.0503 (3)
C4'	0.6755 (2)	0.39556 (11)	0.45473 (8)	0.0202 (2)
H4'	0.6003	0.3430	0.4083	0.024*
C2'	0.5896 (2)	0.45885 (11)	0.61392 (9)	0.0222 (3)
H2'B	0.4716	0.4673	0.6601	0.027*
H2'A	0.6975	0.5197	0.6276	0.027*
N1	0.9382 (2)	0.20760 (9)	0.83973 (8)	0.0292 (3)
N2	1.2305 (2)	0.25492 (11)	0.92835 (8)	0.0306 (3)
H2A	1.1962	0.1985	0.9688	0.037*
H2B	1.3442	0.2976	0.9386	0.037*
C5	1.1535 (2)	0.36764 (12)	0.78583 (10)	0.0275 (3)
H5A	1.2745	0.4160	0.7945	0.033*
C3	0.8409 (2)	0.31633 (11)	0.69690 (8)	0.0209 (3)
C6	1.1088 (2)	0.27585 (11)	0.85080 (9)	0.0236 (3)
C3'	0.51186 (19)	0.46698 (11)	0.51091 (9)	0.0212 (3)
H3'	0.5155	0.5508	0.4892	0.025*
C1'	0.6841 (2)	0.33618 (11)	0.61810 (8)	0.0207 (3)
H1'	0.5678	0.2771	0.6238	0.025*
C5'	0.8338 (2)	0.46924 (11)	0.40046 (9)	0.0246 (3)
H5'A	0.9377	0.4167	0.3691	0.030*
H5'B	0.7596	0.5137	0.3494	0.030*
C2	0.8168 (2)	0.23016 (11)	0.76562 (9)	0.0266 (3)
C4	1.0202 (2)	0.38589 (12)	0.71022 (9)	0.0257 (3)
H4	1.0500	0.4471	0.6658	0.031*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O5'	0.0198 (5)	0.0250 (5)	0.0374 (5)	−0.0012 (4)	−0.0001 (4)	0.0010 (4)
O4'	0.0240 (5)	0.0226 (4)	0.0196 (4)	0.0062 (4)	0.0002 (3)	0.0012 (3)
O3'	0.0161 (5)	0.0239 (4)	0.0461 (6)	−0.0012 (4)	−0.0031 (4)	0.0006 (4)
F1	0.0525 (6)	0.0492 (5)	0.0494 (5)	−0.0340 (5)	−0.0261 (5)	0.0257 (4)
C4'	0.0196 (6)	0.0199 (6)	0.0212 (5)	0.0002 (5)	−0.0037 (5)	0.0001 (4)
C2'	0.0196 (6)	0.0222 (6)	0.0247 (6)	0.0027 (5)	0.0026 (5)	−0.0021 (5)
N1	0.0340 (7)	0.0257 (5)	0.0280 (5)	−0.0071 (5)	−0.0060 (5)	0.0054 (5)
N2	0.0309 (7)	0.0295 (6)	0.0316 (6)	−0.0036 (5)	−0.0088 (5)	0.0051 (5)
C5	0.0224 (6)	0.0317 (7)	0.0284 (6)	−0.0072 (6)	0.0001 (5)	0.0025 (5)
C3	0.0218 (6)	0.0201 (6)	0.0207 (5)	0.0006 (5)	0.0008 (5)	−0.0017 (4)
C6	0.0234 (7)	0.0230 (6)	0.0245 (6)	0.0013 (5)	−0.0009 (5)	−0.0024 (5)
C3'	0.0161 (6)	0.0188 (5)	0.0289 (6)	−0.0008 (4)	−0.0016 (5)	0.0008 (5)
C1'	0.0198 (6)	0.0202 (5)	0.0221 (6)	−0.0026 (5)	0.0014 (5)	0.0002 (4)
C5'	0.0238 (6)	0.0286 (7)	0.0215 (6)	0.0026 (5)	0.0030 (5)	0.0024 (5)
C2	0.0288 (7)	0.0225 (6)	0.0285 (6)	−0.0080 (6)	−0.0046 (5)	0.0020 (5)
C4	0.0255 (7)	0.0265 (6)	0.0251 (6)	−0.0042 (5)	0.0031 (5)	0.0046 (5)

Geometric parameters (Å, º)

O5'—C5'	1.4212 (17)	N1—C6	1.3383 (18)
O5'—H5B	0.840	N2—C6	1.3465 (17)
O4'—C4'	1.4532 (15)	N2—H2A	0.880
O4'—C1'	1.4559 (14)	N2—H2B	0.880
O3'—C3'	1.4278 (15)	C5—C4	1.364 (2)
O3'—H3	0.840	C5—C6	1.4089 (18)
F1—C2	1.3463 (16)	C5—H5A	0.950
C4'—C5'	1.5083 (19)	C3—C2	1.3768 (17)
C4'—C3'	1.5301 (17)	C3—C4	1.3958 (19)
C4'—H4'	1.000	C3—C1'	1.4952 (17)
C2'—C3'	1.5176 (18)	C3'—H3'	1.000
C2'—C1'	1.5182 (18)	C1'—H1'	1.000
C2'—H2'B	0.990	C5'—H5'A	0.990
C2'—H2'A	0.990	C5'—H5'B	0.990
N1—C2	1.3107 (18)	C4—H4	0.950
C5'—O5'—H5B	109.5	N1—C6—C5	121.18 (12)
C4'—O4'—C1'	109.17 (9)	N2—C6—C5	121.96 (12)
C3'—O3'—H3	109.5	O3'—C3'—C2'	112.17 (11)
O4'—C4'—C5'	109.20 (11)	O3'—C3'—C4'	112.32 (10)
O4'—C4'—C3'	106.41 (10)	C2'—C3'—C4'	103.31 (10)
C5'—C4'—C3'	114.24 (10)	O3'—C3'—H3'	109.6
O4'—C4'—H4'	109.0	C2'—C3'—H3'	109.6
C5'—C4'—H4'	109.0	C4'—C3'—H3'	109.6
C3'—C4'—H4'	109.0	O4'—C1'—C3	110.13 (10)
C3'—C2'—C1'	102.70 (10)	O4'—C1'—C2'	103.39 (9)
C3'—C2'—H2'B	111.2	C3—C1'—C2'	115.35 (10)
C1'—C2'—H2'B	111.2	O4'—C1'—H1'	109.2
C3'—C2'—H2'A	111.2	C3—C1'—H1'	109.2
C1'—C2'—H2'A	111.2	C2'—C1'—H1'	109.2
H2'B—C2'—H2'A	109.1	O5'—C5'—C4'	112.53 (10)
C2—N1—C6	116.73 (11)	O5'—C5'—H5'A	109.1
C6—N2—H2A	120.0	C4'—C5'—H5'A	109.1
C6—N2—H2B	120.0	O5'—C5'—H5'B	109.1
H2A—N2—H2B	120.0	C4'—C5'—H5'B	109.1
C4—C5—C6	118.85 (13)	H5'A—C5'—H5'B	107.8
C4—C5—H5A	120.6	N1—C2—F1	113.28 (11)
C6—C5—H5A	120.6	N1—C2—C3	128.34 (13)
C2—C3—C4	113.62 (12)	F1—C2—C3	118.38 (12)
C2—C3—C1'	122.88 (12)	C5—C4—C3	121.29 (12)
C4—C3—C1'	123.46 (11)	C5—C4—H4	119.4
N1—C6—N2	116.83 (12)	C3—C4—H4	119.4
C1'—O4'—C4'—C5'	130.30 (10)	C2—C3—C1'—C2'	122.15 (13)
C1'—O4'—C4'—C3'	6.54 (12)	C4—C3—C1'—C2'	−55.17 (16)
C2—N1—C6—N2	178.23 (12)	C3'—C2'—C1'—O4'	38.53 (13)
C2—N1—C6—C5	0.33 (19)	C3'—C2'—C1'—C3	158.82 (10)
C4—C5—C6—N1	−0.4 (2)	O4'—C4'—C5'—O5'	−63.14 (14)
C4—C5—C6—N2	−178.22 (13)	C3'—C4'—C5'—O5'	55.87 (15)
C1'—C2'—C3'—O3'	86.95 (12)	C6—N1—C2—F1	−179.72 (12)
C1'—C2'—C3'—C4'	−34.23 (12)	C6—N1—C2—C3	−0.4 (2)
O4'—C4'—C3'—O3'	−103.29 (12)	C4—C3—C2—N1	0.5 (2)
C5'—C4'—C3'—O3'	136.14 (12)	C1'—C3—C2—N1	−177.03 (14)
O4'—C4'—C3'—C2'	17.80 (12)	C4—C3—C2—F1	179.81 (12)
C5'—C4'—C3'—C2'	−102.77 (12)	C1'—C3—C2—F1	2.24 (19)
C4'—O4'—C1'—C3	−152.02 (10)	C6—C5—C4—C3	0.6 (2)
C4'—O4'—C1'—C2'	−28.24 (13)	C2—C3—C4—C5	−0.59 (19)
C2—C3—C1'—O4'	−121.32 (13)	C1'—C3—C4—C5	176.96 (12)
C4—C3—C1'—O4'	61.36 (15)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
O5′—H5B···O3′^i	0.84	1.95	2.762 (1)	161
O3′—H3···O4′^ii	0.84	1.98	2.805 (2)	167
N2—H2A···O5′^iii	0.88	2.14	3.002 (2)	165
N2—H2B···O5′^iv	0.88	2.22	3.069 (2)	162

Symmetry codes: (i) x+1, y, z; (ii) x−1/2, −y+1/2, −z+1; (iii) −x+2, y−1/2, −z+3/2; (iv) −x+5/2, −y+1, z+1/2.