Methyl iodide → N-[2,4-Dichloro-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide

HRID 270708Notes

Reaction equation

HRID 270708 reaction equation
[Cl:1][C:2]1[C:7]([C:8]2[C:19](=[O:20])[NH:18][C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[CH:9]=2)=[C:6]([Cl:21])[CH:5]=[CH:4][C:3]=1[NH:22][C:23](=[O:34])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:33])([F:32])[F:31])[CH:25]=1.[H-].[Na+].I[CH3:38]>CN(C=O)C>[Cl:1][C:2]1[C:7]([C:8]2[C:19](=[O:20])[N:18]([CH3:38])[C:11]3[N:12]=[C:13]([S:16][CH3:17])[N:14]=[CH:15][C:10]=3[CH:9]=2)=[C:6]([Cl:21])[CH:5]=[CH:4][C:3]=1[NH:22][C:23](=[O:34])[C:24]1[CH:29]=[CH:28][CH:27]=[C:26]([C:30]([F:32])([F:33])[F:31])[CH:25]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59833903N-[2,4-Dichloro-3-(2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide

Product 1

HCID 59833840N-[2,4-Dichloro-3-(8-methyl-2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamideYield 98%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of N-[2,4-dichloro-3-(2-methylsulfanyl-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidin-6-yl)-phenyl]-3-trifluoromethyl-benzamide (1.14 g, 2.17 mmol) in DMF (35 mL) is slowly added NaH (117.2 mg, 60%, 2.93 mmol) with stirring for 30 minutes a 0° C. Iodomethane (369 mg, 2.60 mmol) is added to above solution with stirring for 40 minutes at 0° C. The solvents are evaporated and diluted with EtOAc and washed with saturated K2CO3, brine and water. The organic layer is dried, filtered and concentrated to give crude product, which is purified by flash silica gel column, eluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N)(93/7), to give the title intermediate as a solid (1.14 g, 98.0%).

Workup

  1. stirringwith stirring for 40 minutes at 0° C
  2. customThe solvents are evaporated
  3. additiondiluted with EtOAc
  4. washwashed with saturated K2CO3, brine and water
  5. customThe organic layer is dried
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give crude product, which
  9. customis purified by flash silica gel column
  10. washeluting with CH2Cl2 (100%) gradient to CH2Cl2/MeOH(NH3, 2N)(93/7)

Sources & evidence

ORD record
ord-98e79c30629d4c1199e1ad98876da7f4
Source dataset
uspto-grants-2008_11
Patent number
US07449582B2

Reaction notes

Loading…