Phenyl thioxochloroformate → O-[(4aS,6R,7S,7aR)-6-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo-[2,3-d]pyrimidin-7-yl}-2-(4-methoxyphenyl)hexahydrocyclopenta[d][1,3]dioxin-7-yl] O-phenyl thiocarbonate

HRID 222148

Reaction equation

HRID 222148 reaction equation
[C@@H:1]1([NH:10][C:11]2[C:12]3[CH:19]=[CH:18][N:17]([C@H:20]4[C@H:36]([OH:37])[C@@H:23]5[O:24][CH:25]([C:28]6[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[CH:30][CH:29]=6)[O:26][CH2:27][C@@H:22]5[CH2:21]4)[C:13]=3[N:14]=[CH:15][N:16]=2)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][CH2:2]1.[CH:38]1[CH:43]=[CH:42][C:41]([O:44][C:45](Cl)=[S:46])=[CH:40][CH:39]=1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:45](=[S:46])([O:44][C:41]1[CH:42]=[CH:43][CH:38]=[CH:39][CH:40]=1)[O:37][C@@H:36]1[C@@H:23]2[O:24][CH:25]([C:28]3[CH:29]=[CH:30][C:31]([O:34][CH3:35])=[CH:32][CH:33]=3)[O:26][CH2:27][C@@H:22]2[CH2:21][C@H:20]1[N:17]1[C:13]2[N:14]=[CH:15][N:16]=[C:11]([NH:10][C@@H:1]3[C:9]4[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=4)[CH2:3][CH2:2]3)[C:12]=2[CH:19]=[CH:18]1

Participants

5

Reactant 2

HCID 70498Phenyl thioxochloroformateHCID 67164240(4aS,6R,7S,7aR)-6-(4-((S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(4-methoxyphenyl)hexahydrocyclopenta[d][1,3]dioxin-7-ol

Product 1

HCID 86614244O-[(4aS,6R,7S,7aR)-6-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo-[2,3-d]pyrimidin-7-yl}-2-(4-methoxyphenyl)hexahydrocyclopenta[d][1,3]dioxin-7-yl] O-phenyl thiocarbonateYield 99%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

(4aS,6R,7S,7aR)-6-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo-[2,3-d]pyrimidin-7-yl}-2-(4-methoxyphenyl)hexahydrocyclopenta[d][1,3]dioxin-7-ol (4.00 g, 8.02 mmol) was dissolved in DCM (169 mL) under an atmosphere of argon and 4-(dimethylamino)-pyridine (2.94 g, 24.1 mmol) was added followed by phenyl chlorothionocarbonate (2.22 mL, 16.0 mmol). The mixture was stirred at rt for 1 hour. The solvent was concentrated in vacuo and purified via silica gel chromatography eluting with a gradient of 20 to 100% EtOAc in hexanes on a column pre-treated with 1% TEA in hexanes to afford the title compound (5.00 g, 99%). LC/MS: Rt=2.34 min, ES+ 636 (AA standard).

Workup

  1. concentrationThe solvent was concentrated in vacuo
  2. custompurified via silica gel chromatography
  3. washeluting with a gradient of 20 to 100% EtOAc in hexanes on a column
  4. additionpre-treated with 1% TEA in hexanes

Sources & evidence

ORD record
ord-2db47a230e724a05b010276de6eec832
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Linked notes

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