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 222174노트

반응식

HRID 222174 반응식
[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]

참가 물질

5

반응물 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

생성물 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 sulfamate수율 66%

시약·촉매·용매 1

HCID 694302-Oxopropiononitrile용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-1a4c561ef49b42be805650c920961d58
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08207177B2

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