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

HRID 222151Notes

Reaction equation

HRID 222151 reaction equation
[C@@H]1(NC2C3C=CN([C@H]4C[C@H:23]([OH:25])[C@H:22](CO)C4)C=3N=CN=2)C2C(=CC=CC=2)CC1.N1C=CN=C1.[Si](Cl)(C(C)(C)C)(C)C.[Si:41]([O:48][CH2:49][C@@H:50]1[CH2:54][C@@H:53]([N:55]2[C:59]3[N:60]=[CH:61][N:62]=[C:63]([NH:64][C@@H:65]4[C:73]5[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=5)[CH2:67][CH2:66]4)[C:58]=3[CH:57]=[CH:56]2)[CH2:52][C@@H:51]1[OH:74])([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42].C(OC(=O)C)(=O)C>CN(C)C1C=CN=CC=1.CN(C=O)C.N1C=CC=CC=1>[C:23]([O:74][C@H:51]1[CH2:52][C@H:53]([N:55]2[C:59]3[N:60]=[CH:61][N:62]=[C:63]([NH:64][C@@H:65]4[C:73]5[C:68](=[CH:69][CH:70]=[CH:71][CH:72]=5)[CH2:67][CH2:66]4)[C:58]=3[CH:57]=[CH:56]2)[CH2:54][C@H:50]1[CH2:49][O:48][Si:41]([C:44]([CH3:47])([CH3:45])[CH3:46])([CH3:42])[CH3:43])(=[O:25])[CH3:22]

Participants

9

Reactant 5

HCID 795ImidazoleHCID 7918Acetic AnhydrideHCID 28928tert-Butyldimethylsilyl chlorideHCID 58944696(1S,2S,4R)-4-(4-((S)-2,3-dihydro-1H-inden-1-ylamino)-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2-(hydroxymethyl)cyclopentanolHCID 66618495(1S,2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentanol

Product 1

HCID 66618132(1S,2S,4R)-2-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl)cyclopentyl acetateYield 86%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 1049PyridineSolventHCID 6228DimethylformamideSolvent

Procedure

(1S,2S,4R)-4-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]-pyrimidin-7-yl}-2-(hydroxymethyl)cyclopentanol (3.00 g, 8.23 mmol), 1H-imidazole (1.68 g, 24.7 mmol) and 4-(dimethylamino)-pyridine (100 mg, 0.818 mmol) were dissolved in DMF (90.0 mL) under an atmosphere of argon and the solution was cooled to 0° C. tert-Butyldimethylsilyl chloride (1.24 g, 8.23 mmol) was added and the mixture was stirred at rt for 2 h. LC/MS indicated complete conversion. The reaction was quenched with saturated aqueous sodium chloride solution (30 mL), extracted with EtOAc (3×50 mL), dried with MgSO4, filtered, and concentrated in vacuo. The remaining DMF was removed under high vacuum. Crude (1S,2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopentanol (3.94 g, 8.23 mmol) and 4-(dimethylamino)-pyridine (100. mg, 0.818 mol) were dissolved in pyridine (70.0 mL) and acetic anhydride (4.66 mL, 49.4 mmol) was added. The mixture was stirred at rt overnight. The solvent was evaporated and the remaining pyridine was removed under high vacuum. The residue was purified via silica gel chromatography eluting with a gradient of 10 to 66% EtOAc in hexanes to afford the title compound (3.66 g, 86%). LC/MS: Rt=2.51 min, ES+ 521 (AA standard).

Workup

  1. additionwas added
  2. customThe reaction was quenched with saturated aqueous sodium chloride solution (30 mL)
  3. extractionextracted with EtOAc (3×50 mL)
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe remaining DMF was removed under high vacuum
  8. stirringThe mixture was stirred at rt overnight
  9. customThe solvent was evaporated
  10. customthe remaining pyridine was removed under high vacuum
  11. customThe residue was purified via silica gel chromatography
  12. washeluting with a gradient of 10 to 66% EtOAc in hexanes

Sources & evidence

ORD record
ord-830928b8bd8b48da8c6da0a13bcf474f
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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