Pyridine → ((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)methyl sulfamate

HRID 222174Notes

Reaction equation

HRID 222174 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])[CH:22]=[CH:21]4)[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.N1C=CC=CC=1.Cl[S:34]([NH2:37])(=[O:36])=[O:35]>C(C#N)(C)=O>[S:34](=[O:36])(=[O:35])([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)[CH:21]=[CH:22]1)[NH2:37]

Participants

5

Reactant 3

HCID 1049PyridineHCID 24499Chlorosulfamic acidHCID 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)methanol

Product 1

HCID 24967723((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)methyl sulfamateYield 66%

Reagents, catalysts & solvents 1

HCID 694302-OxopropiononitrileSolvent2×

Procedure

To a solution of ((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 (35.7 mg, 0.103 mmol) and pyridine (0.0417 mL, 0.515 mmol) in AcCN (1.00 mL) at 0° C. under an atmosphere of nitrogen was added dropwise a 2.00 M solution of chlorosulfonamide in AcCN (0.260 mL, 0.520 mmol, as prepared in 1j). The solution was stirred for 1 hour. The reaction was quenched with saturated aqueous sodium bicarbonate solution and partitioned between water and EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc (2×20 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution, 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 solid (28.9 mg, 66%). 1H NMR (400 MHz, CDCl3, δ): 8.36 (s, 1H), 7.35 (d, J=7.2 Hz, 1H), 7.30-7.18 (m, 3H), 6.89 (d, J=3.6 Hz, 1H), 6.32 (d, J=3.5 Hz, 1H), 6.14-6.12 (m, 1H), 6.04-5.97 (m, 2H), 5.89 (br s, 1H), 4.19 (dd, J=1.2, 6.0 Hz, 2H), 3.43-3.37 (m, 1H), 3.09-3.01 (m, 1H), 2.98-2.90 (m, 1H), 2.77-2.69 (m, 1H), 2.46-2.39 (m, 1H), 2.07-1.93 (m, 3H) ppm. LC/MS: Rt=1.24 min, ES+ 426 (FA standard).

Workup

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

Sources & evidence

ORD record
ord-1a4c561ef49b42be805650c920961d58
Source dataset
uspto-grants-2012_06
Patent number
US08207177B2

Reaction notes

Loading…