Acetic Acid → 2-(2-(3-Tert-butyl-4-((ethylamino)methyl)-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

HRID 1162783ノート

反応式

HRID 1162783 の反応式
[C:1]([C:5]1[C:9]([CH:10]=O)=[CH:8][N:7]([CH2:12][C:13]([NH:15][C:16]2[S:20][C:19]3[CH2:21][CH2:22][CH2:23][CH2:24][C:18]=3[C:17]=2[C:25]([NH:27][CH2:28][CH2:29][OH:30])=[O:26])=[O:14])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(O)(=O)C.[CH2:35]([NH2:37])[CH3:36]>C(Cl)Cl.[Pd]>[C:1]([C:5]1[C:9]([CH2:10][NH:37][CH2:35][CH3:36])=[CH:8][N:7]([CH2:12][C:13]([NH:15][C:16]2[S:20][C:19]3[CH2:21][CH2:22][CH2:23][CH2:24][C:18]=3[C:17]=2[C:25]([NH:27][CH2:28][CH2:29][OH:30])=[O:26])=[O:14])[N:6]=1)([CH3:4])([CH3:2])[CH3:3]

参加物

6

反応物 3

HCID 176Acetic AcidHCID 6341EthylamineHCID 595205022-(2-(3-Tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide

生成物 1

HCID 595204642-(2-(3-Tert-butyl-4-((ethylamino)methyl)-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide収率 45.1%

試薬・触媒・溶媒 2

HCID 23938Palladium触媒HCID 6344Dichloromethane溶媒2 回

実験手順

2-(2-(3-Tert-butyl-4-formyl-1H-pyrazol-1-yl)acetamido)-N-(2-hydroxyethyl)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxamide (1.66 g, 3.84 mmol) was dissolved in DCM (40 mL) and acetic acid (20.98 g, 20 mL, 349 mmol). Ethylamine (2M in THF, 7.68 mL, 15.35 mmol) was added and the mixture was stirred for 90 min. A slurry of palladium on charcoal (10%, 1.51 g, 1.420 mmol) in DCM (30 mL) was added and the mixture hydrogenated at 4 barr for 72 h at 20° C. The catalyst was filtered through dicalite and the dicalite washed with water, DCM and MeOH. All volatiles were removed under reduced pressure and the aqueous residue was basified to pH 8 using sodium bicarbonate. The crude product was extracted with EtOAc. The organics were combined and washed with brine, dried over MgSO4, filtered and concentrated. The crude material was purified by chromatography (DCM, 0-30% MeOH/DCM and 0-20% 7 N NH3 in MeOH/DCM). Concentration in vacuo yielded a white solid (800 mg, 1.73 mmol, 45%).

後処理

  1. waitthe mixture hydrogenated at 4 barr for 72 h at 20° C
  2. filtrationThe catalyst was filtered through dicalite
  3. washthe dicalite washed with water, DCM and MeOH
  4. customAll volatiles were removed under reduced pressure
  5. extractionThe crude product was extracted with EtOAc
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude material was purified by chromatography (DCM, 0-30% MeOH/DCM and 0-20% 7 N NH3 in MeOH/DCM)
  11. concentrationConcentration in vacuo

出典と根拠

ORDレコード
ord-79986d63297a461e8efe21351e1dd174
出典データセット
uspto-grants-2010_10
特許番号
US07820707B2

反応ノート

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