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Diisopropylethylamine → (R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid [(S)-1-(1-pyrimidin-2-yl-cyclopropylcarbamoyl)-ethyl]-amide

HRID 1040565
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HRID 1040565 반응식
[C:1]([C:3]1[CH:31]=[CH:30][C:6]([CH2:7][C@@:8]2([CH3:29])[N:12]3[C:13]([C:16](O)=[O:17])=[CH:14][N:15]=[C:11]3[N:10]([C:19]3[CH:24]=[C:23]([Cl:25])[C:22](F)=[C:21]([Cl:27])[CH:20]=3)[C:9]2=[O:28])=[CH:5][CH:4]=1)#[N:2].[NH2:32][C@@H:33]([CH3:46])[C:34]([NH:36][C:37]1([C:40]2[N:45]=[CH:44][CH:43]=[CH:42][N:41]=2)[CH2:39][CH2:38]1)=[O:35].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[N:41]1[CH:42]=[CH:43][CH:44]=[N:45][C:40]=1[C:37]1([NH:36][C:34]([C@@H:33]([NH:32][C:16]([C:13]2[N:12]3[C@@:8]([CH2:7][C:6]4[CH:30]=[CH:31][C:3]([C:1]#[N:2])=[CH:4][CH:5]=4)([CH3:29])[C:9](=[O:28])[N:10]([C:19]4[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:27])[CH:20]=4)[C:11]3=[N:15][CH:14]=2)=[O:17])[CH3:46])=[O:35])[CH2:38][CH2:39]1
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참가 물질

7

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 58430875(S)-2-Amino-N-(1-pyrimidin-2-yl-cyclopropyl)-propionamideHCID 58431190(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

생성물 1

HCID 58431080
(R)-5-(4-Cyano-benzyl)-7-(3,5-dichloro-phenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carboxylic acid [(S)-1-(1-pyrimidin-2-yl-cyclopropylcarbamoyl)-ethyl]-amide
수율 70.6%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of (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 (85 mg, 0.19 mmol) and (S)-2-Amino-N-(1-pyrimidin-2-yl-cyclopropyl)-propionamide (49 mg, 0.18 mmol) in THF (1.0 mL) and DMF (0.7 mL), was added HATU (80 mg, 0.21 mmol) followed by DIPEA (0.15 mL, 0.88 mmol). The reaction was stirred at room temperature for 20 h. The THF was removed under a stream of N2 and the reaction mixture was purified by reverse phase HPLC. The purified material was then passed through a basic amino group functionalized solid phase extraction cartridge to give 80 mg of the title compound as a solid, m/z 647.34 [M+1]+.

후처리

  1. customThe THF was removed under a stream of N2
  2. customthe reaction mixture was purified by reverse phase HPLC
  3. extractionThe purified material was then passed through a basic amino group functionalized solid phase extraction cartridge

출처 및 근거

ORD 기록
ord-25ca3a12e7004fd4a158b55c93628b10
출처 데이터셋
uspto-grants-2013_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08552205B2

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