Diisopropylethylamine → 6-(cis-2-amino-3,3-difluorocyclohexylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

HRID 711528노트

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HRID 711528 반응식
[Cl:1][C:2]1[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]([F:23])=[C:4](Cl)[N:3]=1.Cl.[F:26][C:27]1([F:35])[CH2:32][CH2:31][CH2:30][C@@H:29]([NH2:33])[C@H:28]1[NH2:34].CCN(C(C)C)C(C)C>C(#N)C>[NH2:34][C@H:28]1[C:27]([F:35])([F:26])[CH2:32][CH2:31][CH2:30][C@H:29]1[NH:33][C:4]1[N:3]=[C:2]([Cl:1])[C:7]2[C:8](=[O:22])[N:9]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[CH:14][C:13]=3[O:20][CH3:21])[CH2:10][C:6]=2[C:5]=1[F:23]

참가 물질

5

반응물 3

HCID 81531DiisopropylethylamineHCID 583175754,6-dichloro-2-[(2,4-dimethoxyphenyl)methyl]-7-fluoro-1H,2H,3H-pyrrolo[3,4-c]pyridin-3-oneHCID 67238749cis-3,3-Difluorocyclohexane-1,2-diamine hydrochloride

생성물 1

HCID 866547266-(cis-2-amino-3,3-difluorocyclohexylamino)-4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one

시약·촉매·용매 1

HCID 6342Acetonitrile용매

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온도
100 °C

실험 절차

A mixture of 4,6-dichloro-2-(2,4-dimethoxybenzyl)-7-fluoro-1H-pyrrolo[3,4-c]pyridin-3(2H)-one (100 mg, 0.269 mmol) and cis-3,3-difluorocyclohexane-1,2-diamine hydrochloride (75 mg, 0.404 mmol) and DIPEA (118 μL, 0.674 mmol) in acetonitrile (449 μL) was stirred at 100° C. for 3 d. The reaction mixture was concentrated to a brown oil and reconstituted in DMF (1 mL). The residue was purified by preparative HPLC, the appropriate fraction was collected, and excess acetonitrile was evaporated. The residue was treated with saturated aq sodium carbonate and extracted with EtOAc (3×20 mL). The organic layers were combined, dried over sodium sulfate, and concentrated to give the title compound as a colorless residue (13.7 mg, 10%). [M+H] calc'd for C22H24ClF3N4O3, 485. found, 485.

후처리

  1. concentrationThe reaction mixture was concentrated to a brown oil
  2. customThe residue was purified by preparative HPLC
  3. customthe appropriate fraction was collected
  4. customexcess acetonitrile was evaporated
  5. additionThe residue was treated with saturated aq sodium carbonate
  6. extractionextracted with EtOAc (3×20 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-7e4acf72347f4499a0dbf9e62de3f416
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09181255B2

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