Hydrochloric Acid → (1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 1185898ノート

反応式

HRID 1185898 の反応式
C(OC([N:8]1[CH2:12][CH:11]([CH2:13][O:14][CH:15]([F:17])[F:16])[CH2:10][CH:9]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=O)(C)(C)C.Cl.[CH3:31][O:32][C:33]([NH:35][CH:36]([CH:40]([CH3:42])[CH3:41])[C:37](O)=[O:38])=[O:34].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)CC)C>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[CH3:31][O:32][C:33](=[O:34])[NH:35][CH:36]([C:37]([N:8]1[CH2:12][CH:11]([CH2:13][O:14][CH:15]([F:17])[F:16])[CH2:10][CH:9]1[C:18]1[NH:19][C:20]([C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)=[CH:21][N:22]=1)=[O:38])[CH:40]([CH3:42])[CH3:41]

参加物

9

反応物 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 138211012-((Methoxycarbonyl)amino)-3-methylbutanoic acidHCID 666207862-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

生成物 1

HCID 66620824(1-{2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester収率 61%

試薬・触媒・溶媒 3

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒

実験手順

2-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-4-difluoromethoxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester was dissolved in DCM (4 mL) and treated with HCl (4.0M in dioxane, 1 mL, 4 mmol). After 2.5 h, the solution was concentrated and the residue was treated with 2-Methoxycarbonylamino-3-methyl-butyric acid (55 mg, 0.315 mmol) and HATU (120 mg, 0.315 mmol). The solids were suspended in DMF (3 mL) and the reaction mixture was cooled to 0° C. before triethylamine (0.25 mL, 1.43 mmol) was added in a dropwise fashion. After 30 min, the mixture was warmed to RT. After another 1 h, it was diluted with EtOAc and washed with saturated aqueous NaHCO3 and brine. Then it was dried over MgSO4, filtered and concentrated. The crude residue was purified by silica column chromatography (60% to 100% EtOAc/Hex) to afford the title compound (92 mg, 61%).

後処理

  1. concentrationthe solution was concentrated
  2. additionwas added in a dropwise fashion
  3. waitAfter 30 min
  4. waitAfter another 1 h
  5. washwashed with saturated aqueous NaHCO3 and brine
  6. dry with materialThen it was dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica column chromatography (60% to 100% EtOAc/Hex)

出典と根拠

ORDレコード
ord-852a42c63e02476797a690e8e7e75d14
出典データセット
uspto-grants-2014_03
特許番号
US08669234B2

反応ノート

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