Dimethylformamide → HCID 71009175, compound

HRID 1626155Notes

Reaction equation

HRID 1626155 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[CH:12]=[C:11]([C@:13]3([CH3:22])[C:18]([F:20])([F:19])[CH2:17][O:16][C:15]([NH2:21])=[N:14]3)[CH:10]=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:23][N:24](C)C=O>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[NH2:21][C:15]1[O:16][CH2:17][C:18]([F:20])([F:19])[C@:13]([C:11]2[CH:10]=[N:9][N:8]([C:4]3[CH:3]=[C:2]([CH:7]=[CH:6][CH:5]=3)[C:23]#[N:24])[CH:12]=2)([CH3:22])[N:14]=1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 71008464HCID 71008464, compound

Product 1

HCID 71009175HCID 71009175, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Procedure

A mixture of (R)-4-(1-(3-bromophenyl)-1H-pyrazol-4-yl)-5,5-difluoro-4-methyl-5,6-dihydro-4H-1,3-oxazin-2-amine (20 mg, 53.9 μmol) (intermediate K7.1), zinc cyanide (3.8 mg, 32.3 μmol) and tetrakis(triphenylphosphine)-palladium(0) (6.23 mg, 5.39 μmol) was heated at 160° C. in N,N-dimethylformamide (0.5 ml) for 30 minutes in a microwave oven. Thereafter, the reaction mixture was evaporated at reduced pressure and purified by preparative HPLC. The 3-[4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-pyrazol-1-yl]-benzonitrile (79% yield) was obtained as a light brown solid. MS (ISP): m/z=318.1 [M+H]+.

Workup

  1. customThereafter, the reaction mixture was evaporated at reduced pressure
  2. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-0d01df3fb1824ba3aa7df38c1ed92b5a
Source dataset
uspto-grants-2014_07
Patent number
US08785436B2

Reaction notes

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