Hydrochloric Acid → 2-((4-(Hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-3,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-one

HRID 1091692Notes

Reaction equation

HRID 1091692 reaction equation
[OH:1][CH2:2][C:3]1[C:4]([C:20]([F:23])([F:22])[F:21])=[N:5][N:6]([CH2:8][C:9]2[NH:10][C:11](=[O:19])[C:12]3[CH:17]=[C:16]([CH3:18])[S:15][C:13]=3[N:14]=2)[CH:7]=1.[H-].[Na+].I[CH3:27].Cl>CN(C=O)C>[OH:1][CH2:2][C:3]1[C:4]([C:20]([F:22])([F:21])[F:23])=[N:5][N:6]([CH2:8][C:9]2[N:10]([CH3:27])[C:11](=[O:19])[C:12]3[CH:17]=[C:16]([CH3:18])[S:15][C:13]=3[N:14]=2)[CH:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 665915302-((4-(Hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one

Product 1

HCID 665912212-((4-(Hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-3,6-dimethylthieno[2,3-d]pyrimidin-4(3H)-oneYield 31%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

2-((4-(Hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one (240 mg, 0.697 mmol) was dissolved in DMF (5 mL). NaH (17 mg, 0.708 mmol) was added and the reaction mixture heated at 60° C. for 1 h, then allowed to cool to RT before cooling further with an ice/salt bath to 0° C. Iodomethane (1.14 g, 0.50 mL, 8.03 mmol) was added in one portion and the reaction mixture stirred at RT for 1 h, then allowed to warm to RT, before standing overnight. The reaction mixture was acidified with 2M HCl and extracted into EtOAc (×3). The EtOAc layer was washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Purification by preparative reverse phase HPLC gave the title product as a white solid (76 mg, 0.213 mmol, 31%).

Workup

  1. temperatureto cool to RT
  2. temperaturebefore cooling further with an ice/salt bath to 0° C
  3. temperatureto warm to RT
  4. waitbefore standing overnight
  5. extractionextracted into EtOAc (×3)
  6. washThe EtOAc layer was washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification by preparative reverse phase HPLC

Sources & evidence

ORD record
ord-8d6b19df417a44358e5b15a521e24ea4
Source dataset
uspto-grants-2012_03
Patent number
US08129397B2

Reaction notes

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