Methylamine → 4-(4-Cyano-2-methylphenyl)-N-methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazoline-3(4H)-carboxamide

HRID 517285Notes

Reaction equation

HRID 517285 reaction equation
[CH:1]([N:4]([CH2:8]C)C(C)C)(C)C.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:12].[O:23]=[C:24]1[NH:33][CH:32]([C:34]2[CH:41]=[CH:40][C:37]([C:38]#[N:39])=[CH:36][C:35]=2[CH3:42])[C:31]2[C:30](=[O:43])[CH2:29][CH2:28][CH2:27][C:26]=2[N:25]1[C:44]1[CH:49]=[CH:48][CH:47]=[C:46]([C:50]([F:53])([F:52])[F:51])[CH:45]=1.CN>CN(C)C1C=CN=CC=1.C(#N)C>[C:38]([C:37]1[CH:40]=[CH:41][C:34]([CH:32]2[C:31]3[C:30](=[O:43])[CH2:29][CH2:28][CH2:27][C:26]=3[N:25]([C:44]3[CH:49]=[CH:48][CH:47]=[C:46]([C:50]([F:53])([F:51])[F:52])[CH:45]=3)[C:24](=[O:23])[N:33]2[C:8]([NH:4][CH3:1])=[O:12])=[C:35]([CH3:42])[CH:36]=1)#[N:39]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 821294-Nitrophenyl chloroformateHCID 867323954-(2,5-Dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-methylbenzonitrile

Product 1

HCID 867324124-(4-Cyano-2-methylphenyl)-N-methyl-2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,5,6,7,8-hexahydroquinazoline-3(4H)-carboxamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

N,N-Diisopropylethylamine (88 μL, 0.51 mmol), 4-dimethylaminopyridine (48 mg, 0.39 mmol) and 4-nitrophenyl chloroformate (78 mg, 0.39 mmol) is added to a solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-3-methylbenzonitrile (example 55, 55 mg, 0.13 mmol) in acetonitrile (1.5 mL), and the mixture is stirred at room temperature over night. Methylamine (2 M in tetrahydrofuran, 97 μL, 0.19 mmol) is added, and the mixture is stirred at room temperature over night and purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 35 mg; ESI mass spectrum [M+H]+=483; Retention time HPLC: 0.74 min (X012_S01).

Workup

  1. stirringthe mixture is stirred at room temperature over night
  2. custompurified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
  3. custom0.74 min (X012_S01)

Sources & evidence

ORD record
ord-a9cee98f5b0a4c188304a8bb6010a152
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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