Methyl bromoacetate → HCID 86732370, compound

HRID 517249Notes

Reaction equation

HRID 517249 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[CH2:40][C:41]([O:43][CH3:44])=[O:42]>CN(C)C=O.C(#N)C>[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[CH2:40][C:41]([O:43][CH3:44])=[O:42])=[CH:19][CH:18]=1)#[N:17]

Participants

6

Reactant 3

HCID 60984Methyl bromoacetateHCID 2724682Lithium diisopropylamideHCID 86732326HCID 86732326, compound

Product 1

HCID 86732370HCID 86732370, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

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, 3.56 g, 6.12 mmol) in a mixture of N,N-dimethyl-formamide (10 mL) and acetonitrile (30 mL) is cooled at 0° C. in an ice bath. Lithium diisopropylamide (2.0 M in tetrahydrofuran, 6.7 mL, 13.4 mmol) is added while the temperature is kept below 5° C. Methyl bromoacetate is added dropwise while the temperature is kept below 10° C. After 1.5 h the ice bath is removed and stiffing is continued over night. The mixture is concentrated under reduced pressure and the residue is purified by preparative HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA). Yield: 1.87 g; ESI mass spectrum [M+H]+=484; Retention time HPLC: 0.95 min (Z018_S04).

Workup

  1. customis kept below 5° C
  2. customis kept below 10° C
  3. customAfter 1.5 h the ice bath is removed
  4. waitstiffing is continued over night
  5. concentrationThe mixture is concentrated under reduced pressure
  6. customthe residue is purified by preparative HPLC (Waters SunFire™-C18, gradient of acetonitrile in water, 0.1% TFA)
  7. custom0.95 min (Z018_S04)

Sources & evidence

ORD record
ord-b2a15f376a054de785ad37d640abad53
Source dataset
uspto-grants-2015_08
Patent number
US09115093B2

Reaction notes

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