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

반응식

HRID 535918 반응식
[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

참가 물질

7

반응물 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

생성물 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)-carboxylate수율 80.4%

시약·촉매·용매 2

HCID 962Water용매HCID 6228Dimethylformamide용매

실험 절차

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%).

후처리

  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

출처 및 근거

ORD 기록
ord-26976d8d425d4c809432bbdffcfe8ef0
출처 데이터셋
uspto-grants-2014_10
특허 번호
US08859538B2

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