Tetrahydrofuran → (R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

HRID 132504노트

반응식

HRID 132504 반응식
[Cl:1][C:2]1[C:10]2[NH:9][N:8]=[CH:7][C:6]=2[C:5]2[CH2:11][N:12]([CH2:18][C:19]([F:22])([F:21])[F:20])[C:13](=[O:17])[C@H:14]([OH:16])[CH2:15][C:4]=2[CH:3]=1.C1COCC1.[H-].[Na+].[O:30]=[C:31]1[C:40]([CH:41]2[CH2:46][CH2:45][N:44]([C:47](OC3C=CC([N+]([O-])=O)=CC=3)=[O:48])[CH2:43][CH2:42]2)=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32]1>>[O:30]=[C:31]1[C:40]([CH:41]2[CH2:42][CH2:43][N:44]([C:47]([O:16][C@H:14]3[C:13](=[O:17])[N:12]([CH2:18][C:19]([F:21])([F:20])[F:22])[CH2:11][C:5]4[C:6]5[CH:7]=[N:8][NH:9][C:10]=5[C:2]([Cl:1])=[CH:3][C:4]=4[CH2:15]3)=[O:48])[CH2:45][CH2:46]2)=[CH:39][C:38]2[C:33](=[CH:34][CH:35]=[CH:36][CH:37]=2)[NH:32]1

참가 물질

5

반응물 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 59732071HCID 59732071, 화합물HCID 693108914-Nitrophenyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate

생성물 1

HCID 11978542(R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate수율 36.1%

실험 절차

(R)-4-chloro-7-hydroxy-9-(2,2,2-trifluoroethyl)-6,7,9,10-tetrahydroazepino[3,4-e]indazol-8(3H)-one (60.0 mg, 0.180 mmol) in THF (10.0 mL, 122 mmol) was added sodium hydride (10.79 mg, 0.450 mmol) followed by 4-nitrophenyl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate (106 mg, 0.270 mmol). After stirring for 48 h, most of the solvent was removed, diluted with dichloromethane (30 mL) and neutralized with 1.0 M HCl. The organic phase was separated, dried (Na2SO4) and the crude product was purified by flash chromatography using 5% MeOH in dichloromethane to give (R)-4-chloro-8-oxo-9-(2,2,2-trifluoroethyl)-3,6,7,8,9,10-hexahydroazepino[3,4-e]indazol-7-yl 4-(2-oxo-1,2-dihydroquinolin-3-yl)piperidine-1-carboxylate (38.00 mg, 0.065 mmol, 36% yield). MS (ESI) 588 (M+H); Rf=2.73.

후처리

  1. customwas removed
  2. additiondiluted with dichloromethane (30 mL)
  3. customThe organic phase was separated
  4. dry with materialdried (Na2SO4)
  5. customthe crude product was purified by flash chromatography

출처 및 근거

ORD 기록
ord-9055f6887dbf4eba8f339813bc2f004b
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384931B2

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