Phosphorus oxychloride → N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine

HRID 1042269

반응식

HRID 1042269 반응식
[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[C:11]([NH:16][C:17]3[C:26]([CH3:27])=[CH:25][CH:24]=[C:23]4[C:18]=3[CH:19]=[CH:20][NH:21][C:22]4=O)=[N:12][CH:13]=[CH:14][CH:15]=2)=[N:3][CH:2]=1.P(Cl)(Cl)([Cl:31])=O>>[N:1]1[C:6]2[NH:7][CH:8]=[CH:9][C:5]=2[C:4]([C:10]2[C:11]([NH:16][C:17]3[C:18]4[CH:19]=[CH:20][N:21]=[C:22]([Cl:31])[C:23]=4[CH:24]=[CH:25][C:26]=3[CH3:27])=[N:12][CH:13]=[CH:14][CH:15]=2)=[N:3][CH:2]=1

참가 물질

3

반응물 2

HCID 24813Phosphorus oxychlorideHCID 596273715-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one

생성물 1

HCID 59627376N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine수율 67.3%

실험 절차

5-(3-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1(2H)-one (750 mg, 2036 μmol) was suspended in phosphorous oxychloride (9.5 mL, 10.2 mmol). The reaction vessel was flushed with N2 and sealed. The reaction was heated in an oil bath for 5 h. The excess reagent was removed in vacuo. The residue was azeotroped with toluene times and then put under high vacuum overnight. The residue was suspended with 50 g of ice. The suspension was neutralized with NaHCO3 (aq., sat.). The resulting mixture was extracted with DCM. The DCM solution was concentrated in vacuo and the residue was purified via flash column on silica (Hexane:EtOAc gradient of 50-10%) to give N-(3-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyridin-2-yl)-1-chloro-6-methylisoquinolin-5-amine as a yellow solid (530 mg, 67% yield). MS (ESI, pos. ion) m/z: 387 [M+H]+

후처리

  1. customThe reaction vessel was flushed with N2
  2. customsealed
  3. temperatureThe reaction was heated in an oil bath for 5 h
  4. customThe excess reagent was removed in vacuo
  5. customThe residue was azeotroped with toluene times
  6. customput under high vacuum overnight
  7. extractionThe resulting mixture was extracted with DCM
  8. concentrationThe DCM solution was concentrated in vacuo
  9. customthe residue was purified via flash column on silica (Hexane:EtOAc gradient of 50-10%)

출처 및 근거

ORD 기록
ord-e3100cf83e314e539dea424865e7c4ac
출처 데이터셋
uspto-grants-2013_10
특허 번호
US08557830B2

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