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 132504ノート

反応式

HRID 132504 の反応式
[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

参加物

5

反応物 4

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

生成物 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-carboxylate収率 36.1%

実験手順

(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.

後処理

  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

出典と根拠

ORDレコード
ord-9055f6887dbf4eba8f339813bc2f004b
出典データセット
uspto-grants-2008_06
特許番号
US07384931B2

反応ノート

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