Dimethylformamide → 4-Methylpyrimidine-2-carbonitrile

HRID 1804583Notes

Reaction equation

HRID 1804583 reaction equation
Cl[C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1.[CH3:9][N:10](C=O)C>[C-]#N.[Zn+2].[C-]#N.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>[C:9]([C:2]1[N:7]=[C:6]([CH3:8])[CH:5]=[CH:4][N:3]=1)#[N:10]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 116296072-Chloro-4-methylpyrimidine

Product 1

HCID 126843244-Methylpyrimidine-2-carbonitrileYield 54%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
180 °C

Procedure

To a solution of 2-chloro-4-methylpyrimidine (1 g, 7.78 mmol) and zinc cyanide (475 mg, 4.04 mmol) in anhydrous DMF (10 ml) was added Pd(PPh3)4 (449 mg, 0.366 mmol) and nitrogen flushed through the mixture for 5 min. The mixture was heated at 180° C. for 30 min in a microwave reactor. The reaction was repeated on the same scale and the reaction mixtures were combined. The mixture was partitioned between EtOAc and water (filtered through celite to remove some insolubles), and the organic layer washed with sat. NaCl, dried over MgSO4, filtered and evaporated. The residue was purified by MPLC (Biotage Horizon: FLASH 25+M) eluent: 100% Hexanes (90 ml), gradient rising from 100% Hexanes to 15% EtOAc in Hexanes (900 ml), then 15% EtOAc in Hexanes (500 ml) to give 1 g of the title compound (54%) as an off-white solid. 1H NMR (CDCl3): 2.62 (s, 3H), 7.42 (d, J 5.1 Hz, 1H), 8.69 (d, J 5.1 Hz, 1H).

Workup

  1. customflushed through the mixture for 5 min
  2. customthe reaction mixtures
  3. customThe mixture was partitioned between EtOAc and water (
  4. filtrationfiltered through celite
  5. customto remove some insolubles), and the organic layer
  6. washwashed with sat. NaCl
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by MPLC (Biotage Horizon: FLASH 25+M) eluent

Sources & evidence

ORD record
ord-7c8fd3b0c9cd4415ad7135cb815413d3
Source dataset
uspto-grants-2013_01
Patent number
US08354403B2

Reaction notes

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