Corey-hopkins reagent → 7-[(1R,4R)-4-({[tert-Butyl(dimethyl)silyl]oxy}methyl)cyclopent-2-en-1-yl]-N-[(1S)-2,3-dihydro-1H-inden-1-yl]-7H-pyrrolo[2,3-d]pyrimidin-4-amine

HRID 222172Notes

Reaction equation

[Si:1]([O:8][CH2:9][C@H:10]1[C@@H:17]2[C@@H:13](OC(=S)O2)[C@H:12]([N:19]2[C:23]3[N:24]=[CH:25][N:26]=[C:27]([NH:28][C@@H:29]4[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[CH2:31][CH2:30]4)[C:22]=3[CH:21]=[CH:20]2)[CH2:11]1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN1CCN(C)P1C1C=CC=CC=1>C1COCC1>[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:11][C@@H:12]([N:19]2[C:23]3[N:24]=[CH:25][N:26]=[C:27]([NH:28][C@@H:29]4[C:37]5[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=5)[CH2:31][CH2:30]4)[C:22]=3[CH:21]=[CH:20]2)[CH:13]=[CH:17]1)([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of (3aR,4S,6R,6aS)-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}tetrahydro-3aH-cyclopenta[d][1,3]dioxole-2-thione (138 mg, 0.257 mmol) in THF (0.860 mL) at 0° C. under an atmosphere of nitrogen was added 1,3-dimethyl-2-phenyl-1,3,2-diazaphospholidine (0.147 mL, 0.793 mmol) dropwise. The solution was stirred for 10 min at 0° C. and then at rt for 5 h. The solvent was removed and the residue was purified by silica gel chromatography eluting with a gradient of 0 to 20% EtOAc in hexanes to afford the title compound as a clear oil (˜70% purity, 81.9 mg, 48%). LC/MS: Rt=2.10 min, ES+ 462 (FA standard).

Workup

waitat rt for 5 h
customThe solvent was removed
customthe residue was purified by silica gel chromatography
washeluting with a gradient of 0 to 20% EtOAc in hexanes

Sources & evidence

ORD record: ord-3fcfec5af0d348bbb9ac82722e59b8eb
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08207177B2

Reaction notes

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