Water → HCID 86732398, compound

HRID 517273Notes

Reaction equation

HRID 517273 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][CH:13]=2)[C:9]2[C:8](=[O:20])[CH2:7][CH2:6][CH2:5][C:4]=2[N:3]1[C:21]1[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=1.C([N-]C(C)C)(C)C.[Li+].Br[CH:40]([F:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42].O>O1CCCC1>[C:16]([C:15]1[CH:14]=[CH:13][C:12]([CH:10]2[C:9]3[C:8](=[O:20])[CH2:7][CH2:6][CH2:5][C:4]=3[N:3]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([C:27]([F:30])([F:28])[F:29])[CH:22]=3)[C:2](=[O:1])[N:11]2[CH:40]([F:46])[C:41]([O:43][CH2:44][CH3:45])=[O:42])=[CH:19][CH:18]=1)#[N:17]

Participants

6

Reactant 4

HCID 962WaterHCID 2724682Lithium diisopropylamideHCID 2733407Acetic acid, 2-bromo-2-fluoro-, ethyl esterHCID 86732326HCID 86732326, compound

Product 1

HCID 86732398HCID 86732398, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-(2,5-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4,5,6,7,8-octahydroquinazolin-4-yl)-benzonitrile (example 1, 200 mg, 0.49 mmol) in tetrahydrofuran (4 mL) is cooled in an ice bath. Lithium diisopropylamide (2 M in tetrahydrofuran, 270 μL, 0.54 mmol) is added, and the mixture is stirred for 15 min. Ethyl 2-bromo-2-fluoroacetate (135 mg, 0.73 mmol) is added, and the mixture is warmed at room temperature and stirred over night. Water is added, and the mixture is extracted twice with dichloromethane. The combined organic layers are concentrated under reduced pressure, and the residue is purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 70 mg; ESI mass spectrum [M+H]+=516; Retention time HPLC: 0.67 min (X012_S01).

Workup

  1. stirringstirred over night
  2. extractionthe mixture is extracted twice with dichloromethane
  3. concentrationThe combined organic layers are concentrated under reduced pressure
  4. customthe residue is purified by preparative HPLC (Waters Xbridge™-C18, gradient of acetonitrile in water, 0.1% TFA)
  5. custom0.67 min (X012_S01)

Sources & evidence

ORD record
ord-03f1321993b54a469fd501ebdd2c692c
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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