Hydrochloric Acid → 1-((6-Methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde

HRID 1091686Notes

Reaction equation

HRID 1091686 reaction equation
[F:1][C:2]([F:11])([F:10])[C:3]1[C:7]([CH:8]=[O:9])=[CH:6][NH:5][N:4]=1.Cl[CH2:13][C:14]1[NH:15][C:16](=[O:24])[C:17]2[CH:22]=[C:21]([CH3:23])[S:20][C:18]=2[N:19]=1.CC(C)([O-])C.[K+].Cl>C1COCC1.CCOC(C)=O.O.CN(C=O)C>[CH3:23][C:21]1[S:20][C:18]2[N:19]=[C:14]([CH2:13][N:5]3[CH:6]=[C:7]([CH:8]=[O:9])[C:3]([C:2]([F:1])([F:10])[F:11])=[N:4]3)[NH:15][C:16](=[O:24])[C:17]=2[CH:22]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 64916832-(Chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-oneHCID 23665647Potassium tert-butoxideHCID 178519884HCID 178519884, compound

Product 1

HCID 866303971-((6-Methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehydeYield 58.4%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

3-(Trifluoromethyl)-1H-pyrazole-4-carbaldehyde (3.82 g, 23.3 mmol) and 2-(chloromethyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one (5.00 g, 23.3 mmol) were suspended in THF:DMF (180 mL:20 mL) and potassium tert-butoxide (5.23 g, 46.6 mmol) added. The resulting mixture was stirred at RT for 18 h. The mixture was then diluted with EtOAc (500 mL) and shaken with water (200 mL). The separated aqueous phase was acidified to pH 5 with dilute HCl solution and reshaken with the organic layer. The separated organics were then washed with brine (2×200 mL) and dried over MgSO4 before concentration in vacuo. Purification by flash column chromatography-silica gel and elution with 50% isohexane:EtOAc, then EtOAc, gave the desired product as a pale yellow solid (4.65 g, 13.6 mmol, 58%).

Workup

  1. washThe separated organics were then washed with brine (2×200 mL)
  2. dry with materialdried over MgSO4 before concentration in vacuo
  3. customPurification
  4. washby flash column chromatography-silica gel and elution with 50% isohexane

Sources & evidence

ORD record
ord-383d8b75bd524d6aa21db07431ec43db
Source dataset
uspto-grants-2012_03
Patent number
US08129397B2

Reaction notes

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