Dimethylformamide → HCID 86723896, compound

HRID 576787Notes

Reaction equation

HRID 576787 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([C:13]3[C:14](=[O:35])[N:15]([C@@H:31]([CH3:34])[CH2:32][OH:33])[C:16](=[O:30])[N:17]([C:20]4[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=4)[C:18]=3[CH3:19])=[CH:11][CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:36][N:37](C)C=O>[C-]#N.[Zn+2].[C-]#N.[Zn].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:33][CH2:32][C@@H:31]([N:15]1[C:14](=[O:35])[C:13]([C:12]2[N:8]([C:5]3[CH:6]=[CH:7][C:2]([C:36]#[N:37])=[CH:3][CH:4]=3)[N:9]=[CH:10][CH:11]=2)=[C:18]([CH3:19])[N:17]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([C:26]([F:29])([F:28])[F:27])[CH:21]=2)[C:16]1=[O:30])[CH3:34]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 86723897HCID 86723897, compound

Product 1

HCID 86723896HCID 86723896, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-5-(1-(4-bromophenyl)-1H-pyrazol-5-yl)-3-(1-hydroxypropan-2-yl)-6-methyl-1-(3-(trifluoromethyl)phenyl)pyrimidin-2,4(1H,3H)-dione (prepared in Example 122) (5.0 mg) in N,N-dimethy formamide (1.0 ml) were added zinc cyanide (10.3 mg), zinc dust (1.2 mg) and tetrakis(triphenylphosphine)palladium (5.3 mg) and the resulting mixture was stirred at 120° C. for four hours. The reaction mixture was filtered and thereto was added ethyl acetate (50 ml) and the mixture was washed with water (10 ml) and saturated saline (10 ml), dried over anhydrous sodium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate) to afford (S)-4-(5-(3-(1-hydroxypropan-2-yl)-6-methyl-2,4-dioxo-1-(3-(trifluoromethyl)phenyl)-1,2,3,4-tetrahydropyrimidin-5-yl)-1H-pyrazol-1-yl)benzonitrile (1.9 mg) as white solid.

Workup

  1. filtrationThe reaction mixture was filtered
  2. additionwas added ethyl acetate (50 ml)
  3. washthe mixture was washed with water (10 ml) and saturated saline (10 ml)
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate)

Sources & evidence

ORD record
ord-90b3b7f37e404c4ab2be4394c1f85b56
Source dataset
uspto-grants-2015_05
Patent number
US09040516B2

Reaction notes

Loading…