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 1040565Notes

Reaction equation

HRID 1040565 reaction equation
[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

Participants

7

Reactant 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

Product 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]-amideYield 70.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

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]+.

Workup

  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

Sources & evidence

ORD record
ord-25ca3a12e7004fd4a158b55c93628b10
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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