Ethanol → 1-(1-methylethyl)-N-{[6-methyl-2-oxo-4-(phenylmethyl)-1,2-dihydro-3-pyridinyl]methyl}-1H-indazole-4-carboxamide

HRID 1476386ノート

反応式

HRID 1476386 の反応式
Br[C:2]1[CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]2[C:19](=[O:32])[NH:20][C:21]([CH3:31])=[CH:22][C:23]=2[CH2:24][C:25]2[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=2)=[O:15])[C:5]2[CH:6]=[N:7][N:8]([CH:11]([CH3:13])[CH3:12])[C:9]=2[CH:10]=1.C(O)C.C(N(CC)CC)C>[Pd].C1COCC1>[CH3:13][CH:11]([N:8]1[C:9]2[CH:10]=[CH:2][CH:3]=[C:4]([C:14]([NH:16][CH2:17][C:18]3[C:19](=[O:32])[NH:20][C:21]([CH3:31])=[CH:22][C:23]=3[CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)=[O:15])[C:5]=2[CH:6]=[N:7]1)[CH3:12]

参加物

6

反応物 3

HCID 702EthanolHCID 8471TriethylamineHCID 545965546-bromo-1-(1-methylethyl)-N-{[6-methyl-2-oxo-4-(phenylmethyl)-1,2-dihydro-3-pyridinyl]methyl}-1H-indazole-4-carboxamide

生成物 1

HCID 545965551-(1-methylethyl)-N-{[6-methyl-2-oxo-4-(phenylmethyl)-1,2-dihydro-3-pyridinyl]methyl}-1H-indazole-4-carboxamide

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 8028Tetrahydrofuran溶媒

実験手順

To a dried 50 mL round bottom flask was placed 10% Pd/C (0.020 g, 9.63 mol), followed by degassing with N2. Added about 5 mL EtOH and then added 6-bromo-1-(1-methylethyl)-N-{[6-methyl-2-oxo-4-(phenylmethyl)-1,2-dihydro-3-pyridinyl]methyl}-1H-indazole-4-carboxamide (0.095 g, 0.193 mmol) and ethanol (5 mL) and THF (1 mL). Next added in triethylamine (0.081 mL, 0.578 mmol) via syringe. The mixture was stirred under atmosphere of hydrogen (balloon) for 6 h. The mixture was purged with nitrogen and then diluted with DCM (10 mL) and a small amount of celite, After stirring for 10 min, the contents were then filtered through analytical grade celite and washed with 10% MeOH/DCM, EtOH, and then DCM. The filtrate was concentrated in vacuo and dried under hi vacuum overnight. The crude product was purified by silica gel chromatography (eluent: 5-50% gradient of 10% methanol in dichloromethane and dichloromethane). The final product was concentrated from MTBE and dried in vacuum oven at 45° C. for 18 h. The title compound was collected as a white solid (0.75 g, 92% yield); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.48 (d, J=6.57 Hz, 6H) 2.10 (s, 3H) 3.98 (s, 2H) 4.43 (d, J=5.05 Hz, 2H) 5.03 (quin, J=6.63 Hz, 1H) 5.81 (s, 1H) 7.15-7.31 (m, 5H) 7.39 (t, J=7.71 Hz, 1H) 7.52 (d, J=6.82 Hz, 1H) 7.85 (d, J=8.34 Hz, 1H) 8.34 (s, 1H) 8.50 (t, J=5.05 Hz, 1H) 11.61 (s, 1H); MS (ES) [M+H]+ 415.0.

後処理

  1. customTo a dried 50 mL round bottom flask was placed
  2. customby degassing with N2
  3. additionAdded about 5 mL EtOH
  4. customThe mixture was purged with nitrogen
  5. additiondiluted with DCM (10 mL)
  6. stirringa small amount of celite, After stirring for 10 min
  7. filtrationthe contents were then filtered through analytical grade celite
  8. washwashed with 10% MeOH/DCM, EtOH
  9. concentrationThe filtrate was concentrated in vacuo
  10. customdried under hi vacuum overnight
  11. customThe crude product was purified by silica gel chromatography (eluent: 5-50% gradient of 10% methanol in dichloromethane and dichloromethane)
  12. concentrationThe final product was concentrated from MTBE
  13. customdried in vacuum oven at 45° C. for 18 h

出典と根拠

ORDレコード
ord-95f1292859a0409ba2a7bd4129869699
出典データセット
uspto-grants-2015_04
特許番号
US09018382B2

反応ノート

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