4-Nitrophenyl chloroformate → HCID 57917591, compound

HRID 1878325Notes

Reaction equation

HRID 1878325 reaction equation
[NH2:1][C:2]1[CH:29]=[CH:28][C:5]([C:6]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[C:17]([CH:25]=[CH:26][CH:27]=3)[C:18]([NH:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:10][CH2:9]2)=[O:7])=[CH:4][CH:3]=1.Cl[C:31](OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].[O:43]1[CH:47]=[CH:46][C:45]([NH2:48])=[N:44]1>ClCCl>[C:21]([NH:20][C:18](=[O:19])[C:17]1[CH:25]=[CH:26][CH:27]=[C:15]([CH2:14][N:11]2[CH2:12][CH2:13][N:8]([C:6](=[O:7])[C:5]3[CH:28]=[CH:29][C:2]([NH:1][C:31]([NH:48][C:45]4[CH:46]=[CH:47][O:43][N:44]=4)=[O:32])=[CH:3][CH:4]=3)[CH2:9][CH2:10]2)[CH:16]=1)([CH3:24])([CH3:23])[CH3:22]

Participants

5

Reactant 3

HCID 821294-Nitrophenyl chloroformateHCID 18102163-IsoxazolamineHCID 66877986HCID 66877986, compound

Product 1

HCID 57917591HCID 57917591, compoundYield 60%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

3-((4-(4-Aminobenzoyl)piperazin-1-yl)methyl)-N-tert-butylbenzamide (0.152 mmol, 60 mg) was dissolved in dichloromethane (12 mL) and a solution of 4-nitrophenyl chloroformate (0.152 mmol, 30.7 mg) in dichloromethane (20 mL) was added dropwise. The reaction was stirred for 2 hours at room temperature. Isoxazol-3-amine (1.521 mmol, 128 mg) was added and the resulting mixture was stirred at room temperature overnight. The reaction mixture was concentrated under vacuum and the residue dissolved in dichloromethane. This solution was loaded onto a strong cation exchange column and washed with dichloromethane (20 mL) then methanol (20 mL). The column was then eluted with 2M ammonia in methanol (20 mL) and the eluent was concentrated under vacuum. The residue was purified by acidic reverse phase HPLC and lyophilised to give the title compound (46 mg).

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. concentrationThe reaction mixture was concentrated under vacuum
  3. dissolutionthe residue dissolved in dichloromethane
  4. washwashed with dichloromethane (20 mL)
  5. washThe column was then eluted with 2M ammonia in methanol (20 mL)
  6. concentrationthe eluent was concentrated under vacuum
  7. customThe residue was purified by acidic reverse phase HPLC

Sources & evidence

ORD record
ord-95e0d14ebde24f7aaf90a92649802621
Source dataset
uspto-grants-2012_11
Patent number
US08314091B2

Reaction notes

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