Diisopropylethylamine → (S)-tert-butyl 3-bromo-1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate

HRID 535918

反応式

HRID 535918 の反応式
[Br:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12])[CH2:10][C:5]2=[C:4]([C:18]([OH:20])=O)[N:3]=1.[CH3:21][NH:22][C:23](=[O:30])[C@H:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[NH2:25].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.O>[Br:1][C:2]1[N:6]2[CH2:7][CH2:8][N:9]([C:11]([O:13][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:12])[CH2:10][C:5]2=[C:4]([C:18](=[O:20])[NH:25][C@@H:24]([C:26]([CH3:29])([CH3:28])[CH3:27])[C:23]([NH:22][CH3:21])=[O:30])[N:3]=1

参加物

7

反応物 4

HCID 81531DiisopropylethylamineHCID 445856(2S)-2-Amino-N,3,3-trimethylbutanamideHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 576354283-bromo-7-[(tert-butoxy)carbonyl]-5H,6H,7H,8H-imidazo[1,5-a]pyrazine-1-carboxylic acid

生成物 1

HCID 57635359(S)-tert-butyl 3-bromo-1-(3,3-dimethyl-1-(methylamino)-1-oxobutan-2-ylcarbamoyl)-5,6-dihydroimidazo[1,5-a]pyrazine-7(8H)-carboxylate収率 80.4%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

実験手順

Acid Intermediate 1I (0.62 g, 1.79 mmol) was dissolved in DMF and L-tert-Leucine methylamide (0.31 g, 2.14 mmol) was added followed by DIEA (0.94 mL, 5.37 mmol). The resulting mixture was stirred for 20 minutes, HBTU (0.75 g, 1.97 mmol) was added in one portion and the mixture was stirred overnight. The mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed successively with water, then brine, and dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by normal phase chromatography, eluting with a 0-10% methanol/DCM gradient to provide product Intermediate 1J as an off-white solid (0.68 g, 80%).

後処理

  1. stirringthe mixture was stirred overnight
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed successively with water
  4. dry with materialbrine, and dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by normal phase chromatography
  8. washeluting with a 0-10% methanol/DCM gradient

出典と根拠

ORDレコード
ord-26976d8d425d4c809432bbdffcfe8ef0
出典データセット
uspto-grants-2014_10
特許番号
US08859538B2

関連ノート

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