Dimethylacetamide → HCID 67281509, compound

HRID 515498Notes

Reaction equation

HRID 515498 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@H:8]2[CH2:14][N:13]([C:15]3[N:16]([CH3:28])[C:17](=[O:27])[CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][N:24]=[CH:23][N:22]=4)[N:20]=3)[CH2:12][CH2:11][CH2:10][O:9]2)[CH:5]=[CH:6][CH:7]=1.[CH3:29][N:30](C)C(=O)C>[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>[C:29]([C:2]1[CH:3]=[C:4]([C@@H:8]2[CH2:14][N:13]([C:15]3[N:16]([CH3:28])[C:17](=[O:27])[CH:18]=[C:19]([C:21]4[CH:26]=[CH:25][N:24]=[CH:23][N:22]=4)[N:20]=3)[CH2:12][CH2:11][CH2:10][O:9]2)[CH:5]=[CH:6][CH:7]=1)#[N:30]

Participants

5

Reactant 2

HCID 31374DimethylacetamideHCID 46936116HCID 46936116, compound

Product 1

HCID 67281509HCID 67281509, compoundYield 85%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
110 °C

Procedure

To a solution of (S)-2-[2-(3-bromophenyl)-[1,4]oxazepan-4-yl]-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (A079) (1.0 g, 2.26 mmol) in N,N-dimethylacetamide (7.5 ml) was added zinc cyanide (0.292 g, 2.49 mmol) and tetrakis(triphenylphosphine) palladium(0) (523 mg, 0.452 mmol) at room temperature under nitrogen atmosphere. The mixture was stirred at 110° C. for 8 hours. The resulting mixture was filtered through a pad of Celite and partitioned between aqueous sodium hydrogen carbonate and chloroform. The organic layer was washed with water, dried over sodium sulfate and concentrated in vacuo. The residue was purified by silica gel column chromatography (eluant: chloroform/acetone=4/1) to afford (R)-2-[2-(3-cyanophenyl)-[1,4]oxazepan-4-yl]-1-methyl-1H-[4,4′]bipyrimidinyl-6-one (A039) as pale yellow solid (745 mg, 85%).

Workup

  1. filtrationThe resulting mixture was filtered through a pad of Celite
  2. custompartitioned between aqueous sodium hydrogen carbonate and chloroform
  3. washThe organic layer was washed with water
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by silica gel column chromatography (eluant: chloroform/acetone=4/1)

Sources & evidence

ORD record
ord-cc77d7edc23c4f4e8941aaa0ba813ddb
Source dataset
uspto-grants-2015_08
Patent number
US09108957B2

Reaction notes

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