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

HRID 1878343Notes

Reaction equation

HRID 1878343 reaction equation
Cl[C:2](OC1C=CC([N+]([O-])=O)=CC=1)=[O:3].[NH2:14][C:15]1[CH:42]=[CH:41][C:18]([C:19]([N:21]2[CH2:26][CH2:25][N:24]([CH2:27][C:28]3[CH:29]=[C:30]([CH:38]=[CH:39][CH:40]=3)[C:31]([NH:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:23][CH2:22]2)=[O:20])=[C:17]([F:43])[CH:16]=1.[CH:44]1([CH2:47][NH2:48])[CH2:46][CH2:45]1>C(#N)C>[C:34]([NH:33][C:31](=[O:32])[C:30]1[CH:38]=[CH:39][CH:40]=[C:28]([CH2:27][N:24]2[CH2:25][CH2:26][N:21]([C:19](=[O:20])[C:18]3[CH:41]=[CH:42][C:15]([NH:14][C:2]([NH:48][CH2:47][CH:44]4[CH2:46][CH2:45]4)=[O:3])=[CH:16][C:17]=3[F:43])[CH2:22][CH2:23]2)[CH:29]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 3

HCID 75646CyclopropanemethanamineHCID 821294-Nitrophenyl chloroformateHCID 579176473-((4-(4-Amino-2-fluorobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide

Product 1

HCID 57917593N-tert-Butyl-3-((4-(4-(3-(cyclopropylmethyl)ureido)-2-fluorobenzoyl)piperazin-1-yl)methyl)benzamideYield 8.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

4-Nitrophenyl chloroformate (59 mg, 0.29 mmol) was added to a solution of 3-((4-(4-amino-2-fluorobenzoyl)piperazin-1-yl)methyl)-N-tertbutylbenzamide (100 mg, 0.24 mmol) in acetonitrile (10 mL). After stirring at room temperature for 1 hour, cyclopropylmethylamine (126 μL, 1.21 mmol) was added. After 2 hours stirring, the reaction was purified by strong cation exchange chromatography, eluting macroporous polystyrene sulfonic acid with 2N ammonia in methanol. The resulting solution was concentrated under vacuum and purified by basic reverse phase HPLC to afford the title compound as a white solid (10 mg).

Workup

  1. stirringAfter 2 hours stirring
  2. customthe reaction was purified by strong cation exchange chromatography
  3. washeluting macroporous polystyrene sulfonic acid with 2N ammonia in methanol
  4. concentrationThe resulting solution was concentrated under vacuum
  5. custompurified by basic reverse phase HPLC

Sources & evidence

ORD record
ord-e3eb9176b36346c1a72d1df8eb0f5c65
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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