Triethylamine → N-tert-Butyl-3-((4-(3-chloro-4-(3-(cyclopropylmethyl)ureido)-2-fluorobenzoyl)piperazin-1-yl)methyl)benzamide

HRID 1878368Notes

Reaction equation

HRID 1878368 reaction equation
[C:1](=[O:12])(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl.C(N(CC)CC)C.[NH2:20][C:21]1[CH:48]=[CH:47][C:24]([C:25]([N:27]2[CH2:32][CH2:31][N:30]([CH2:33][C:34]3[CH:35]=[C:36]([CH:44]=[CH:45][CH:46]=3)[C:37]([NH:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:29][CH2:28]2)=[O:26])=[C:23]([F:49])[C:22]=1[Cl:50].[CH:51]1([CH2:54][NH2:55])[CH2:53][CH2:52]1>ClCCl>[C:40]([NH:39][C:37](=[O:38])[C:36]1[CH:44]=[CH:45][CH:46]=[C:34]([CH2:33][N:30]2[CH2:29][CH2:28][N:27]([C:25](=[O:26])[C:24]3[CH:47]=[CH:48][C:21]([NH:20][C:1]([NH:55][CH2:54][CH:51]4[CH2:53][CH2:52]4)=[O:12])=[C:22]([Cl:50])[C:23]=3[F:49])[CH2:32][CH2:31]2)[CH:35]=1)([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 75646CyclopropanemethanamineHCID 94429TriphosgeneHCID 579176553-((4-(4-Amino-3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide

Product 1

HCID 25191629N-tert-Butyl-3-((4-(3-chloro-4-(3-(cyclopropylmethyl)ureido)-2-fluorobenzoyl)piperazin-1-yl)methyl)benzamideYield 24.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of bis(trichloromethyl) carbonate (0.128 mmol, 38.1 mg) in dichloromethane (6 mL) was added a mixture of triethylamine (0.867 mmol, 0.121 mL, 88 mg) and 3-((4-(4-amino-3-chloro-2-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide (0.347 mmol, 155 mg) in dichloromethane (6 mL). The mixture was heated to reflux for 2 hours before being cooled to room temperature. Cyclopropylmethylamine (0.694 mmol, 0.060 mL, 49.3 mg) was added and the mixture stirred for 2 hours. After this time the reaction was concentrated under reduced pressure and purified by silica chromatography to yield the title compound (17 mg).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 2 hours
  3. concentrationAfter this time the reaction was concentrated under reduced pressure
  4. custompurified by silica chromatography

Sources & evidence

ORD record
ord-c7ed0f1d26974540b89f39ae8a217605
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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