Imidazole → (1S,2R,3S,5R)-3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-5-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentane-1,2-diol

HRID 222170Notes

Reaction equation

HRID 222170 reaction equation
[C@@H:1]1([NH:10][C:11]2[C:12]3[CH:19]=[CH:18][N:17]([C@@H:20]4[CH2:24][C@@H:23]([CH2:25][OH:26])[C@@H:22]([OH:27])[C@H:21]4[OH:28])[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.[Si:29](Cl)([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30].N1C=CN=C1>CN(C=O)C>[Si:29]([O:26][CH2:25][C@@H:23]1[CH2:24][C@@H:20]([N:17]2[C:13]3[N:14]=[CH:15][N:16]=[C:11]([NH:10][C@@H:1]4[C:9]5[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=5)[CH2:3][CH2:2]4)[C:12]=3[CH:19]=[CH:18]2)[C@H:21]([OH:28])[C@@H:22]1[OH:27])([C:32]([CH3:35])([CH3:34])[CH3:33])([CH3:31])[CH3:30]

Participants

5

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chloride2×HCID 66618091(1R,2S,3R,5S)-3-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol

Product 1

HCID 66618228(1S,2R,3S,5R)-3-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-5-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentane-1,2-diol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of (1R,2S,3R,5S)-3-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}-5-(hydroxymethyl)cyclopentane-1,2-diol (166 mg, 0.436 mmol, as prepared in Example 15a), tert-butyldimethylsilyl chloride (69.0 mg, 0.458 mmol), 1H-imidazole (44.6 mg, 0.654 mmol) in DMF (2.00 mL) was stirred under an atmosphere of nitrogen. After 2 h additional tert-butyldimethylsilyl chloride (6.00 mg, 0.0365 mmol) was added and the solution was stirred for 1 hour. The reaction was quenched with water and extracted with EtOAc. The combined organics were washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. The residue filtered through a plug of silica gel eluting with 60% EtOAc in hexanes to afford the title compound as an off white solid (179 mg, 83%). LC/MS: Rt=1.51 min, ES+ 495 (FA standard).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with EtOAc
  3. washThe combined organics were washed with water and saturated aqueous sodium chloride solution
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. filtrationThe residue filtered through a plug of silica gel eluting with 60% EtOAc in hexanes

Sources & evidence

ORD record
ord-6ea9061fd5ac40d8b1d554d79e08c896
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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