Water → tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate

HRID 516004

반응식

HRID 516004 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.[NH2:25][C@@H:26]1[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]1[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36].C(N(C(C)C)CC)(C)C.O>C(#N)C.CCOC(C)=O>[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]([NH:25][C@@H:26]2[CH2:31][CH2:30][CH2:29][CH2:28][C@@H:27]2[NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[N:3]=1

참가 물질

7

반응물 4

HCID 962WaterHCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 583175754,6-dichloro-2-[(2,4-dimethoxyphenyl)methyl]-7-fluoro-1H,2H,3H-pyrrolo[3,4-c]pyridin-3-one

생성물 1

HCID 86654712tert-Butyl (1S,2R)-2-(4-chloro-2-(2,4-dimethoxybenzyl)-7-fluoro-3-oxo-2,3-dihydro-1H-pyrrolo[3,4-c]pyridin-6-ylamino)cyclohexylcarbamate수율 46.6%

시약·촉매·용매 2

HCID 6342Acetonitrile용매HCID 8857Ethyl Acetate용매

반응 조건

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 (4.8 g, 12.93 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (4.16 g, 19.40 mmol) and diisopropylethylamine (3.39 mL, 19.40 mmol) in ACN (20 mL) was stirred at 100° C. for 3 days. Water and EtOAc were added and the aqueous phase was extracted with EtOAc. The organic phases were combined, washed with brine, dried over MgSO4, and evaporated. The residue was purified by chromatography on SiO2 (Hexane/EtOAc=1/1) to give the title compound as a brown amorphous solid (3.31 g, 46.6%). 1H NMR (500 MHz, CDCl3) δ ppm 1.35-2.02 (m, 17 H), 3.80 (s, 3 H), 3.84 (s, 3 H), 4.01 (br s, 1 H), 4.20 (s, 2H), 4.23 (br s, 1 H), 4.66 (s, 2 H), 4.91 (br s, 1 H), 6.40-6.52 (m, 2 H), 7.20-7.28 (m, 1 H). [M+H] calc'd for C27H34ClFN4O5, 549; found, 549.

후처리

  1. extractionthe aqueous phase was extracted with EtOAc
  2. washwashed with brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by chromatography on SiO2 (Hexane/EtOAc=1/1)

출처 및 근거

ORD 기록
ord-49f1f6d573d441a593b2279a478fc290
출처 데이터셋
uspto-grants-2015_08
특허 번호
US09108970B2

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