Diisopropylethylamine → 4-{[(R)-5-(4-cyanobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-4-(1-pyridin-2-yl-cyclopropyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1040551Notes

Reaction equation

HRID 1040551 reaction equation
[C:1]([C:3]1[CH:30]=[CH:29][C:6]([CH2:7][C@@:8]2([CH3:28])[N:12]3[C:13]([C:16]([OH:18])=O)=[CH:14][N:15]=[C:11]3[N:10]([C:19]3[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=3)[C:9]2=[O:27])=[CH:5][CH:4]=1)#[N:2].[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41]([NH2:56])([C:44](=[O:55])[NH:45][C:46]2([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=3)[CH2:48][CH2:47]2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:33])[CH3:32].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>CN(C=O)C.O>[C:31]([O:35][C:36]([N:38]1[CH2:43][CH2:42][C:41]([NH:56][C:16]([C:13]2[N:12]3[C@@:8]([CH2:7][C:6]4[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:30][CH:29]=4)([CH3:28])[C:9](=[O:27])[N:10]([C:19]4[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=4)[C:11]3=[N:15][CH:14]=2)=[O:18])([C:44](=[O:55])[NH:45][C:46]2([C:49]3[CH:54]=[CH:53][CH:52]=[CH:51][N:50]=3)[CH2:48][CH2:47]2)[CH2:40][CH2:39]1)=[O:37])([CH3:34])([CH3:32])[CH3:33]

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 58430912(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 acidHCID 584310604-Amino-4-(1-pyridin-2-yl-cyclopropylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 584311224-{[(R)-5-(4-cyanobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-4-(1-pyridin-2-yl-cyclopropyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl esterYield 99.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a mixture of (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 (80 mg, 0.18 mmol) and 4-amino-4-(1-pyridin-2-yl-cyclopropylcarbamoyl)-piperidine-1-carboxylic acid tert-butyl ester (74 mg, 0.20 mmol) in DMF (1 mL) was added HATU (76 mg, 0.19 mmol) and diisopropylethylamine (47 mg, 0.36 mmol). The reaction was stirred at room temperature for 7 h. After addition of water (10 mL) the mixture was extracted with EtOAc (2×15 mL). The organic layer was washed with brine and dried over Na2SO4. The solvent was removed in vacuo and the remaining residue was purified via reverse phase HPLC to afford 4-{[(R)-5-(4-cyanobenzyl)-7-(3,5-dichlorophenyl)-5-methyl-6-oxo-6,7-dihydro-5H-imidazo[1,2-a]imidazole-3-carbonyl]-amino}-4-(1-pyridin-2-yl-cyclopropyl-carbamoyl)-piperidine-1-carboxylic acid tert-butyl ester as a white solid (140 mg), m/z 784.9 [M+1]+.

Workup

  1. extractionwas extracted with EtOAc (2×15 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed in vacuo
  5. customthe remaining residue was purified via reverse phase HPLC

Sources & evidence

ORD record
ord-2d21546f3e164abaa71756a4de0fbf59
Source dataset
uspto-grants-2013_10
Patent number
US08552205B2

Reaction notes

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