Ammonia methanol → 2',3'-Dideoxy-3'-thiacytidine

HRID 1856635Notes

Reaction equation

C(O[C:4]1[CH:9]=[CH:8][N:7]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[S:12][CH2:11]2)[C:6](=[O:17])[N:5]=1)C.[NH3:18].CO>>[OH:16][CH2:15][C@@H:13]1[S:12][CH2:11][C@H:10]([N:7]2[CH:8]=[CH:9][C:4]([NH2:18])=[N:5][C:6]2=[O:17])[O:14]1

Participants

Reactant 2

HCID 21705897Ammonia methanol

HCID 57014494HCID 57014494, compound

Product 1

HCID 733392',3'-Dideoxy-3'-thiacytidineYield 89%

Conditions

Temperature: 70 °C

Procedure

A solution of (2S*,5R*)-4-ethoxy-1-[2-(hydroxymethyl)-1,3-oxathiolan-5-yl]pyrimidin-2-one (0.21g) in ammonia/methanol (8 mL of methanol saturated with ammonia gas at 0° C. for 45 minutes) was placed in a steel bomb with a teflon liner, sealed and heated at 70° C. for 18 hours. Solvent was evaporated in vacuo and the residue subjected to flash chromatography to give the desired product (0.16g, 89%) as a white solid: mp 184-185° C.; 1H NMR (DMSO-d6): δ3.00 (dd, J=11.8, 5.0 Hz, 1H), 3.38 (dd, J=11.8, 5.5 Hz, 1H), 3.63-3.80 (m, 2H), 5.15 (t, J=4.5 Hz, 1H), 5.30 (t, J=6.0 Hz, 1H), 5.70 (d, J=7.3 Hz, 1H); 6.18 (t, J=5.0 Hz, 1H), 7.20 (brd, 2H, NH2), 7.79 (d, J=7.3 Hz, 1H); MS m/z 229.8 (M+1, 4%), 112(100%). Anal. Calcd. for C8H11N3O3S: C, 41.91; H, 4.84; N, 18.33; S, 13.99. Found: C, 41.97; H, 4.83; N, 18.24; S, 13.93

Workup

customsealed
customSolvent was evaporated in vacuo

Sources & evidence

ORD record: ord-10eff025fe334c40a77936389a71e0c1
Source dataset: uspto-grants-2000_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06143748

Reaction notes

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