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

HRID 1878366Notes

Reaction equation

HRID 1878366 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]([Cl:49])[C:22]=1[F: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]([F:50])[C:23]=3[Cl:49])[CH2:32][CH2:31]2)[CH:35]=1)([CH3:43])([CH3:42])[CH3:41]

Participants

6

Reactant 4

HCID 8471Triethylamine2×HCID 75646CyclopropanemethanamineHCID 94429TriphosgeneHCID 579176283-((4-(4-Amino-2-chloro-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide

Product 1

HCID 57917615N-tert-Butyl-3-((4-(2-chloro-4-(3-(cyclopropylmethyl)ureido)-3-fluorobenzoyl)piperazin-1-yl)methyl)benzamideYield 193.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of bis(trichloromethyl) carbonate (0.076 mmol, 22.60 mg) in dichloromethane (3 mL) was added triethylamine (40 mL) and 3-((4-(4-amino-2-chloro-3-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide (0.206 mmol, 92 mg) in dichloromethane (3 mL). The reaction mixture was heated to reflux for 2 hours. After this time the reaction was allowed to cool to room temperature and cyclopropylmethylamine (35 μl, 0.412 mmol) and triethylamine (35 μl) were added. After 30 minutes stirring, the volatiles were removed under reduced pressure and the crude residue was purified by silica chromatography (eluting with 5% methanol in dichloromethane) to yield the title compound (80 mg).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux for 2 hours
  3. customthe volatiles were removed under reduced pressure
  4. customthe crude residue was purified by silica chromatography (eluting with 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-c0e6eeff1a524151a737c7c2ce05d9d3
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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