Dimethylformamide → HCID 70157614, compound

HRID 1278579Notes

Reaction equation

HRID 1278579 reaction equation
[CH2:1]([N:3]([CH2:38][CH3:39])[C:4]([C:6]1[CH:7]=[N:8][C:9]([C:12]2([C:24]3[CH:25]=[C:26](OS(C(F)(F)F)(=O)=O)[CH:27]=[CH:28][CH:29]=3)[CH2:17][CH2:16][N:15]([CH2:18][CH:19]([CH3:23])[CH2:20][CH2:21][CH3:22])[CH2:14][CH2:13]2)=[N:10][CH:11]=1)=[O:5])[CH3:2].[CH3:40][N:41](C=O)C>[C-]#N.[Zn+2].[C-]#N>[CH2:38]([N:3]([CH2:1][CH3:2])[C:4]([C:6]1[CH:11]=[N:10][C:9]([C:12]2([C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([C:40]#[N:41])[CH:25]=3)[CH2:13][CH2:14][N:15]([CH2:18][CH:19]([CH3:23])[CH2:20][CH2:21][CH3:22])[CH2:16][CH2:17]2)=[N:8][CH:7]=1)=[O:5])[CH3:39]

Participants

4

Reactant 2

HCID 6228DimethylformamideHCID 88182968HCID 88182968, compound

Product 1

HCID 70157614HCID 70157614, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 11186Zinc cyanide (Zn(CN)2)Catalyst

Conditions

Temperature
80 °C

Procedure

A stirring solution of Trifluoro-methanesulfonic acid 3-[4-(5-diethylcarbamoyl-pyrimidin-2-yl)-1-(2-methyl-pentyl)-piperidin-4-yl]-phenyl ester (260 mg, 0.46 mmol), zinc cyanide (Zn(CN)2) (81 mg, 0.69 mmol) and tetrakistriphenylphosphine palladium (0) (266 mg, 0.23 mmol) in 8 mL DMF was cooled to −78° C. and de-oxygenated via a freeze-thaw process. The reaction mixture was heated to 80° C. for 1.5 hours, cooled to room temperature and filtered. The resulting solution was partitioned between EtOAc and water, the layers were separated and the aqueous layer was extracted with EtOAc (3×15 mL). The combined organic layers were dried and concentrated. The resulting crude material was purified by flash chromatography to afford 173 mg (84%) of the desired nitrile. 1HNMR (400 MHz, CDCl3) δ 8.69 (s, 2H), 7.64-7.59 (comp, 1H), 7.41-7.29 (comp, 3H), 3.51-3.49 (comp, 2H), 3.25-3.23 (comp, 2H), 2.97-2.94 (comp, 2H), 2.66 (br s, 2H), 2.27-2.25 (comp, 2H), 2.05-1.90 (comp, 4H), 1.57-1.55 (comp, 1H), 1.31-1.15 (comp, 9H), 0.99-0.95 (comp, 1H), 0.83-0.81 (comp, 6H); MS (M+1) 448.3.

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered
  3. customThe resulting solution was partitioned between EtOAc and water
  4. customthe layers were separated
  5. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
  6. customThe combined organic layers were dried
  7. concentrationconcentrated
  8. customThe resulting crude material was purified by flash chromatography

Sources & evidence

ORD record
ord-90ffdfd07ae942f1b8e4f6e71c21ce23
Source dataset
uspto-grants-2002_09
Patent number
US06444679B1

Reaction notes

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