Methylamine → 4-(4-Cyano-2-methylsulfanyl-phenyl)-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,4,5,6,7,8-hexahydro-2H-quinazoline-3-carboxylic acid methylamide

HRID 59647Notes

Reaction equation

HRID 59647 reaction equation
[O:1]=[C:2]1[NH:11][CH:10]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[S:20][CH3:21])[C:9]2[C:8](=[O:22])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]1[C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=1.[CH:33]([N:36]([CH:39](C)C)CC)(C)C.C1C([N+]([O-])=[O:49])=CC=C([Cl-]C([O-])=O)C=1.CN.C(=O)(OC1C=CC([N+]([O-])=O)=CC=1)N>C(#N)C.CN(C)C1C=CN=CC=1>[CH3:33][NH:36][C:39]([N:11]1[CH:10]([C:12]2[CH:19]=[CH:18][C:15]([C:16]#[N:17])=[CH:14][C:13]=2[S:20][CH3:21])[C:9]2[C:8](=[O:22])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]([C:23]2[CH:28]=[CH:27][CH:26]=[C:25]([C:29]([F:32])([F:31])[F:30])[CH:24]=2)[C:2]1=[O:1])=[O:49]

Participants

7

Reactant 4

HCID 6329MethylamineHCID 81531DiisopropylethylamineHCID 1699564-Nitrophenyl hydrogen carbonimidateHCID 1186929024-[2,5-Dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-3-methylsulfanyl-benzonitrile2×

Product 1

HCID 1186928894-(4-Cyano-2-methylsulfanyl-phenyl)-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,4,5,6,7,8-hexahydro-2H-quinazoline-3-carboxylic acid methylamide

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6342AcetonitrileSolvent

Procedure

To a mixture of 4-[2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydroquinazoline-4-yl]-3-methylsulfanyl-benzonitrile (INTERMEDIATE 6; 82 mg; 0.179 mmol) and diisopropylethylamine (100 μL; 0.588 mmol) in acetonitrile (1 mL) is added 4-nitrophenylchloroformate (170 mg; 0.843 mmol) and 4-dimethylaminopyridine (210 mg; 1.719 mmol) in little portions over 19 h at room temperature. Methylamine (1M in THF; 1 mL; 1.00 mmol) is added to the mixture containing the 4-nitro-phenyl carbamate intermediate and the mixture is stirred at room temperature for 30 min. The reaction mixture is purified by reversed phase HPLC (Sunfire, gradient of acetonitrile in water, 0.1% TFA). Yield: 63 mg. ESI mass spectrum: [M+H]+=515; Retention time HPLC: 1.11 min (Z018_S04).

Workup

  1. customThe reaction mixture is purified by reversed phase HPLC (Sunfire, gradient of acetonitrile in water, 0.1% TFA)
  2. custom1.11 min (Z018_S04)

Sources & evidence

ORD record
ord-12a9c1b6f8d44747b0b733980a112753
Source dataset
uspto-grants-2016_09
Patent number
US09440930B2

Reaction notes

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