Triethylamine → 2-[4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-1H-imidazol-1-YL]carbonyl]-1-piperazinyl]-1-(4-morpholinyl)ethanone

HRID 2425602

Reaction equation

HRID 2425602 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30](Cl)=[O:31])[C@H:13]([C:23]3[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=3)[C@H:14]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[N:43]1([C:49](=[O:57])[CH2:50][N:51]2[CH2:56][CH2:55][NH:54][CH2:53][CH2:52]2)[CH2:48][CH2:47][O:46][CH2:45][CH2:44]1>C(Cl)Cl>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:12]([C:30]([N:54]3[CH2:53][CH2:52][N:51]([CH2:50][C:49]([N:43]4[CH2:44][CH2:45][O:46][CH2:47][CH2:48]4)=[O:57])[CH2:56][CH2:55]3)=[O:31])[C@H:13]([C:23]3[CH:24]=[CH:25][C:26]([Cl:29])=[CH:27][CH:28]=3)[C@H:14]([C:16]3[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=3)[N:15]=2)=[C:7]([O:33][CH2:34][CH3:35])[CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1006221-(Morpholinocarbonylmethyl)piperazineHCID 57732375(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride

Product 1

HCID 117218402-[4-[[(4S,5R)-4,5-Bis(4-chlorophenyl)-2-[4-(1,1-dimethylethyl)-2-ethoxyphenyl]-4,5-dihydro-1H-imidazol-1-YL]carbonyl]-1-piperazinyl]-1-(4-morpholinyl)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of (4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl chloride (7.967 g, 15.03 mmol, example 11) in methylene chloride (60 mL) cooled to 0° C. were added triethylamine (4.19 mL) and 1-morpholin-4-yl-2-piperazin-1-yl-ethanone (3.366 g, 15.78 mmol, Oakwood Products), respectively. The ice bath was removed, and the reaction mixture was stirred at room temperature for 30 min. The reaction was monitored by thin layer chromatography (silica gel, 20% ethyl acetate in hexane). The reaction mixture was concentrated to dryness, and the crude residue was purified by flash column chromatography (silica gel, eluting with 0.1% triethylamine in ethyl acetate) to give 2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone as white foam. The white foam was taken in 100 ml of ethyl acetate then filtered. Hydrogen chloride (18.04 mL, 1 M solution in diethyl ether) was added dropwise to the filtrate. The white solids formed were filtered off and dried in vacuo to give 2-{4-[(4S,5R)-2-(4-tert-butyl-2-ethoxy-phenyl)-4,5-bis-(4-chloro-phenyl)-4,5-dihydro-imidazole-1-carbonyl]-piperazin-1-yl}-1-morpholin-4-yl-ethanone hydrochloride (9.3 g). HR-MS (ES, m/z) calculated for C38H46N5O4Cl2 [(M+H)+] 706.2922, observed 706.2917.

Workup

  1. customThe ice bath was removed
  2. concentrationThe reaction mixture was concentrated to dryness
  3. customthe crude residue was purified by flash column chromatography (silica gel, eluting with 0.1% triethylamine in ethyl acetate)

Sources & evidence

ORD record
ord-19ddfdef3544488b84091671a31c3607
Source dataset
uspto-grants-2011_06
Patent number
US07964724B2

Linked notes

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