Pyridine → (1S,2S,4R)-4-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]-pyrimidin-7-yl}-2-(hydroxymethyl)cyclopentyl acetate

HRID 222152

Reaction equation

HRID 222152 reaction equation
[C:1]([O:4][C@H:5]1[CH2:9][C@H:8]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:19][C@@H:20]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH2:22][CH2:21]4)[C:13]=3[CH:12]=[CH:11]2)[CH2:7][C@H:6]1[CH2:29][O:30][Si](C(C)(C)C)(C)C)(=[O:3])[CH3:2].N1C=CC=CC=1.F.N1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C1COCC1>[C:1]([O:4][C@H:5]1[CH2:9][C@H:8]([N:10]2[C:14]3[N:15]=[CH:16][N:17]=[C:18]([NH:19][C@@H:20]4[C:28]5[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=5)[CH2:22][CH2:21]4)[C:13]=3[CH:12]=[CH:11]2)[CH2:7][C@H:6]1[CH2:29][OH:30])(=[O:3])[CH3:2]

Participants

7

Reactant 5

HCID 1049PyridineHCID 64774Pyridine, hydrofluoride (1:1)HCID 516892Sodium BicarbonateHCID 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 acetateHCID 178435178HCID 178435178, compound

Product 1

HCID 66618460(1S,2S,4R)-4-{4-[(1S)-2,3-Dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]-pyrimidin-7-yl}-2-(hydroxymethyl)cyclopentyl acetateYield 80.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

(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 (3.66 g, 7.03 mmol) was dissolved in THF (31.3 mL) and pyridine (31.3 mL, 387 mmol) in a polypropylene vial and the solution was cooled to 0° C. Pyridine hydrofluoride (8.61 mL, 95.6 mmol) was added dropwise and the mixture was stirred at rt for 1 hour. The resulting solution was added dropwise into a solution of saturated aqueous sodium bicarbonate (150 mL), extracted with EtOAc (3×50 mL), dried with MgSO4, filtered, and concentrated in vacuo. The residue was purified via silica gel chromatography eluting with a gradient of 0 to 10% MeOH in DCM to afford the title compound (2.30 g, 80%). LC/MS: Rt=1.64 min, ES+ 407 (AA standard).

Workup

  1. extractionextracted with EtOAc (3×50 mL)
  2. dry with materialdried with MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via silica gel chromatography
  6. washeluting with a gradient of 0 to 10% MeOH in DCM

Sources & evidence

ORD record
ord-88540a7c5556462287951b80405af45e
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Linked notes

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