Tributylstannane → 4-(Benzylsulfanyl)-7-[(4aS,6R,7aS)-2-(4-methoxyphenyl)hexahydrocyclopenta[d]-[1,31dioxin-6-yl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 222156Notes

Reaction equation

C(=S)(OC1C=CC=CC=1)O[C@@H:3]1[C@@H:7]2[O:8][CH:9]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][CH:13]=3)[O:10][CH2:11][C@@H:6]2[CH2:5][C@H:4]1[N:20]1[C:24]2[N:25]=[CH:26][N:27]=[C:28]([S:29][CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:23]=2[CH:22]=[CH:21]1.N(C(C)(C)C#N)=NC(C)(C)C#N.C([SnH](CCCC)CCCC)CCC>C1(C)C=CC=CC=1>[CH2:30]([S:29][C:28]1[C:23]2[CH:22]=[CH:21][N:20]([C@H:4]3[CH2:3][C@@H:7]4[O:8][CH:9]([C:12]5[CH:13]=[CH:14][C:15]([O:18][CH3:19])=[CH:16][CH:17]=5)[O:10][CH2:11][C@@H:6]4[CH2:5]3)[C:24]=2[N:25]=[CH:26][N:27]=1)[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

Conditions

Temperature: 140 °C

Procedure

To a solution of O-[(4aS,6R,7S,7aR)-6-[4-(benzylsulfanyl)-7H-pyrrolo[2,3-d]-pyrimidin-7-yl]-2-(4-methoxyphenyl)hexahydrocyclopenta[d][1,3]dioxin-7-yl] O-phenyl thiocarbonate (1.77 g, 1.98 mmol) in toluene (91.0 mL) was added 2,2′-azo-bis-isobutyronitrile (67.7 mg, 0.404 mmol) and tri-n-butyltin hydride (1.11 mL, 4.00 mmol) under an atmosphere of nitrogen. The yellow solution was heated to reflux at 140° C. After 2 h, the reaction mixture was cooled, silica gel was added, and the solvent was removed in vacuo. Silica gel chromatography eluting with a gradient of 0 to 100% EtOAc in hexanes afforded the title compound as a semi-solid (800 mg, 85%). LC/MS: Rt=2.38 min, ES+ 475 (FA standard).

Workup

temperatureThe yellow solution was heated
temperaturethe reaction mixture was cooled
additionsilica gel was added
customthe solvent was removed in vacuo
washSilica gel chromatography eluting with a gradient of 0 to 100% EtOAc in hexanes

Sources & evidence

ORD record: ord-ebdb9940ba6f4cdf84b1a05a85321a22
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207177B2

Reaction notes

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