Triethylamine → rac-2-{4-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide

HRID 1894315Notes

Reaction equation

HRID 1894315 reaction equation
[C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35](Cl)=[O:36])[C:16]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)([CH3:27])[C:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl.Cl.[N:47]1([CH2:53][C:54]([NH2:56])=[O:55])[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1>ClCCl>[C:1]([C:5]1[N:10]=[C:9]([O:11][CH2:12][CH3:13])[C:8]([C:14]2[N:15]([C:35]([N:50]3[CH2:51][CH2:52][N:47]([CH2:53][C:54]([NH2:56])=[O:55])[CH2:48][CH2:49]3)=[O:36])[C@@:16]([C:28]3[CH:29]=[CH:30][C:31]([Cl:34])=[CH:32][CH:33]=3)([CH3:27])[C@@:17]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)([CH3:19])[N:18]=2)=[CH:7][N:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 177503752-(Piperazin-1-yl)acetamide dihydrochlorideHCID 76588520rac-(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride

Product 1

HCID 25261822rac-2-{4-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamideYield 78.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

rac-(4S*,5R*)-2-(2-tert-Butyl-4-ethoxy-pyrimidin-5-yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl chloride (110 mg, 0.2 mmol) was added to the mixture of triethylamine (140 uL, 1.0 mmol) and 2-piperazin-1-yl-acetamide dihydrochloride (52 mg, 0.24 mmol, Matrix Scientific) in 3 mL of dichloromethane at 0° C. The mixture was allowed to react for 16 h then concentrated to dryness under reduced pressure. Purification of the crude residue by flash column chromatography (40 g of silica gel, eluting with a gradient of 5 to 100% of 9:1 ethyl acetate-methanol and ethyl acetate) provided 105 mg of rac-2-{4-[(4S*,5R*)-2-(2-tert-butyl-4-ethoxy-pyrimidin-5yl)-4,5-bis-(4-chloro-phenyl)-4,5-dimethyl-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-acetamide as white solids.

Workup

  1. customto react for 16 h
  2. concentrationthen concentrated to dryness under reduced pressure
  3. customPurification of the crude residue by flash column chromatography (40 g of silica gel
  4. washeluting with a gradient of 5 to 100% of 9:1 ethyl acetate-methanol and ethyl acetate)

Sources & evidence

ORD record
ord-333439933c7c4873ac218e5cedebf044
Source dataset
uspto-grants-2013_08
Patent number
US08513239B2

Reaction notes

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