Pyridine, hydrofluoride (1:1) → ((1R,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopent-2-en-1-yl)methanol

HRID 222173Notes

Reaction equation

HRID 222173 reaction equation
[Si]([O:8][CH2:9][C@@H:10]1[CH2:14][C@@H:13]([N:15]2[C:19]3[N:20]=[CH:21][N:22]=[C:23]([NH:24][C@@H:25]4[C:33]5[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=5)[CH2:27][CH2:26]4)[C:18]=3[CH:17]=[CH:16]2)[CH:12]=[CH:11]1)(C(C)(C)C)(C)C.F.N1C=CC=CC=1>N1C=CC=CC=1.C1COCC1>[C@@H:25]1([NH:24][C:23]2[C:18]3[CH:17]=[CH:16][N:15]([C@@H:13]4[CH2:14][C@@H:10]([CH2:9][OH:8])[CH:11]=[CH:12]4)[C:19]=3[N:20]=[CH:21][N:22]=2)[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH2:27][CH2:26]1

Participants

5

Reactant 2

HCID 64774Pyridine, hydrofluoride (1:1)HCID 666179807-[(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

Product 1

HCID 66618064((1R,4R)-4-{4-[(1S)-2,3-dihydro-1H-inden-1-ylamino]-7H-pyrrolo[2,3-d]pyrimidin-7-yl}cyclopent-2-en-1-yl)methanolYield 57.9%

Reagents, catalysts & solvents 2

HCID 1049PyridineSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 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 (81.9 mg, 0.178 mmol) in pyridine (0.800 mL) and THF (0.800 mL) at 0° C. under an atmosphere of nitrogen was added dropwise pyridine hydrofluoride (0.0500 mL, 0.555 mol). The solution was warmed to rt and stirred overnight. The reaction was quenched with saturated aqueous sodium bicarbonate solution and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel chromatography eluting with a gradient of 0 to 5% MeOH in DCM to afford the title compound as a white solid (˜70% purity, 35.7 mg, 41%). LC/MS: Rt=1.03 min, ES+ 347 (FA standard).

Workup

  1. customThe reaction was quenched with saturated aqueous sodium bicarbonate solution
  2. additiondiluted with EtOAc
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc (3×20 mL)
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of 0 to 5% MeOH in DCM

Sources & evidence

ORD record
ord-5d9966b8ed6446418d1828e7018117c8
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

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