Cesium carbonate → 3-Methanesulfonyl-4-[3-oxetan-3-ylmethyl-2,5-dioxo-1-(3-trifluoromethyl-phenyl)-1,2,3,4,5,6,7,8-octahydro-quinazolin-4-yl]-benzonitrile

HRID 59661Notes

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

Participants

Conditions

Temperature: 50 °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, 150 mg, 0.28 mmol) in DMF (3.0 mL) is added cesium carbonate (178 mg, 0.55 mmol) and 3-bromomethyl-oxetane (83 mg, 0.55 mmol) and the mixture is stirred at 50° C. over night. The reaction mixture is diluted with DMF and water and purified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 35.5 mg; ESI mass spectrum [M+H]+=560; Retention time HPLC: 1.04 min (Z018_S04).

Workup

custompurified by reversed phase HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
custom1.04 min (Z018_S04)

Sources & evidence

ORD record: ord-118b54c3ec944e2cb89de1af4b5b124c
Source dataset: uspto-grants-2016_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09440930B2

Reaction notes

Loading…