Cesium carbonate → Acetic acid 2-[4-(4-cyano-2-methanesulfonyl-phenyl)-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,4,5,6,7,8-hexahydro-2H-quinazolin-3-yl]-ethyl ester

HRID 59662Notes

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]([CH3:23])(=[O:22])=[O:21])[C:9]2[C:8](=[O:24])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]1[C:25]1[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:34])([F:33])[F:32])[CH:26]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Br[CH2:42][CH2:43][O:44][C:45](=[O:47])[CH3:46]>CN(C=O)C>[C:16]([C:15]1[CH:18]=[CH:19][C:12]([CH:10]2[C:9]3[C:8](=[O:24])[CH2:7][CH2:6][CH2:5][C:4]=3[N:3]([C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([C:31]([F:33])([F:34])[F:32])[CH:26]=3)[C:2](=[O:1])[N:11]2[CH2:42][CH2:43][O:44][C:45](=[O:47])[CH3:46])=[C:13]([S:20]([CH3:23])(=[O:22])=[O:21])[CH:14]=1)#[N:17]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 4-[2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-3-methanesulfonyl-benzonitrile (INTERMEDIATE 18, 200 mg, 0.41 mmol) in DMF (4 mL) is added cesium carbonate (266 mg, 0.82 mmol) and 2-bromoethylacetate (91.0 μL, 0.82 mmol) and the mixture is stirred at 60° C. for 3 days. The mixture is purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 60.0 mg; ESI mass spectrum [M+H]+=576; Retention time HPLC: 1.07 min (Z018_S04).

Workup

customThe mixture is purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
custom1.07 min (Z018_S04)

Sources & evidence

ORD record: ord-70d147d10dd1474287f0b9342f6aab0d
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440930B2

Reaction notes

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