Diisopropylethylamine → (R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid{1-[(R)-1-(5-bromo-pyridin-2-yl)-ethylcarbamoyl]-cyclopropyl}-amide

HRID 2038783노트

반응식

HRID 2038783 반응식
[C:1]([C:3]1[CH:37]=[CH:36][C:6]([CH2:7][C@@:8]2([CH3:35])[N:12]3[C:13]([C:16]([NH:18][C:19]4([C:22]([OH:24])=O)[CH2:21][CH2:20]4)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:25]3[CH:30]=[C:29]([Cl:31])[C:28]([F:32])=[C:27]([Cl:33])[CH:26]=3)[C:9]2=[O:34])=[CH:5][CH:4]=1)#[N:2].Cl.Cl.[Br:40][C:41]1[CH:42]=[CH:43][C:44]([C@H:47]([NH2:49])[CH3:48])=[N:45][CH:46]=1.C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[Br:40][C:41]1[CH:42]=[CH:43][C:44]([C@H:47]([NH:49][C:22]([C:19]2([NH:18][C:16]([C:13]3[N:12]4[C@@:8]([CH2:7][C:6]5[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:37][CH:36]=5)([CH3:35])[C:9](=[O:34])[N:10]([C:25]5[CH:26]=[C:27]([Cl:33])[C:28]([F:32])=[C:29]([Cl:31])[CH:30]=5)[C:11]4=[N:15][CH:14]=3)=[O:17])[CH2:21][CH2:20]2)=[O:24])[CH3:48])=[N:45][CH:46]=1

참가 물질

6

반응물 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 673908991-{[(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acidHCID 68378980(r)-1-(5-Bromo-pyridin-2-yl)-ethylamine dihydrochloride

생성물 1

HCID 68378962(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid{1-[(R)-1-(5-bromo-pyridin-2-yl)-ethylcarbamoyl]-cyclopropyl}-amide수율 98%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

A suspension of 1-{[(R)-5-(4-cyano-benzyl)-7-(3,5-dichloro-4-fluoro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-cyclopropanecarboxylic acid, (500 mg, 0.92 mmol), (R)-1-(5-bromo-pyridin-2-yl)-ethylamine dihydrochloride (303 mg, 1.11 mmol) and diisopropylethylamine (0.640 mL, 3.69 mmol) in 4 mL of DMF was stirred at room temperature for 10 min HATU (386 mg, 1.01 mmol) was added, and the clear yellow reaction mixture was stirred at room temperature for 3 h. The reaction mixture was partitioned between 75 mL of ethyl acetate and 25 mL of water. The organic phase was washed with 2×25 mL of 5% aqueous NaCl solution and 25 mL of brine, dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, eluting with 0-3% MeOH in CH2Cl2, to provide 653 mg (98%) of title compound as a yellow foam, m/z 726.4 [M+1]+.

후처리

  1. additionwas added
  2. customThe reaction mixture was partitioned between 75 mL of ethyl acetate and 25 mL of water
  3. washThe organic phase was washed with 2×25 mL of 5% aqueous NaCl solution and 25 mL of brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash chromatography on silica gel
  8. washeluting with 0-3% MeOH in CH2Cl2

출처 및 근거

ORD 기록
ord-41c68f8e9d6140db823bf3e7531f90b8
출처 데이터셋
uspto-grants-2013_11
특허 번호
US08575360B2

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