Hydrochloric Acid → (1-{3-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester

HRID 417386

反応式

HRID 417386 の反応式
C(O[C:6]([N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=3)=[CH:17][N:18]=2)[CH:12]2[CH2:26][CH:9]1[CH2:10][CH2:11]2)=[O:7])(C)(C)C.Cl.[CH3:28][O:29][C:30]([NH:32][CH:33]([CH:37]([CH3:39])[CH3:38])C(O)=O)=[O:31].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>CO.O1CCOCC1>[CH3:28][O:29][C:30](=[O:31])[NH:32][CH:33]([C:6]([N:8]1[CH:13]([C:14]2[NH:15][C:16]([C:19]3[CH:24]=[CH:23][C:22]([Br:25])=[CH:21][CH:20]=3)=[CH:17][N:18]=2)[CH:12]2[CH2:26][CH:9]1[CH2:10][CH2:11]2)=[O:7])[CH:37]([CH3:39])[CH3:38]

参加物

8

反応物 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 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 596109073-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

生成物 1

HCID 66620573(1-{3-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester収率 89%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
50 °C

実験手順

To a solution of 3-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (1.0 g, 2.4 mmol) in methanol (20 mL) was added 4.0 M solution of HCl in dioxane (4.0 mL, excess). The mixture was stirred for 3 hours at 50° C. and concentrated under reduced pressure. The residue was treated with ether to remove excess HCl. The obtained white solid was dissoved in DMF (20 mL). To the solution was added 2-methoxycarbonylamino-3-methyl-butyric acid (0.46 g, 2.6 mmol), HATU (1.0 g, 2.6 mmol) and N,N-diisopropylethylamine (2.5 mL, 14.4 mmol). The mixture was stirred at ambient for 2 hours, and then the volatile component was removed in vacuo. The residue was dissolved in ethyl acetate (200 mL), washed with 1 N NaOH solution, water and brine, dried over MgSO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product as a white solid (1.0 g, 89%). m/z 475.1, 477.1 (M+H)+.

後処理

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was treated with ether
  3. customto remove excess HCl
  4. stirringThe mixture was stirred at ambient for 2 hours
  5. customthe volatile component was removed in vacuo
  6. dissolutionThe residue was dissolved in ethyl acetate (200 mL)
  7. washwashed with 1 N NaOH solution, water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe obtained residue was purified by flash chromatography

出典と根拠

ORDレコード
ord-8e1b106b077f4e9faeda4704ce7bbd49
出典データセット
uspto-grants-2012_01
特許番号
US08088368B2

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