Water → 2-((4-(1-Hydroxyethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl)methyl)-6-methylthieno[2,3-d]pyrimidin-4(3H)-one

HRID 1091690Notes

Reaction equation

[CH3:1][C:2]1[S:23][C:5]2[N:6]=[C:7]([CH2:11][N:12]3[CH:16]=[C:15]([CH:17]=[O:18])[C:14]([C:19]([F:22])([F:21])[F:20])=[N:13]3)[NH:8][C:9](=[O:10])[C:4]=2[CH:3]=1.[CH3:24][Mg]Br.O>C(OCC)C>[OH:18][CH:17]([C:15]1[C:14]([C:19]([F:21])([F:22])[F:20])=[N:13][N:12]([CH2:11][C:7]2[NH:8][C:9](=[O:10])[C:4]3[CH:3]=[C:2]([CH3:1])[S:23][C:5]=3[N:6]=2)[CH:16]=1)[CH3:24]

Participants

Conditions

Temperature: -78 °C

Procedure

1-((6-Methyl-4-oxo-3,4-dihydrothieno[2,3-d]pyrimidin-2-yl)methyl)-3-(trifluoromethyl)-1H-pyrazole-4-carbaldehyde (100 mg, 0.292 mmol) was dissolved in diethyl ether (10 mL) and cooled to −78° C. with a dry ice/acetone bath. The reaction was performed under a nitrogen atmosphere. Methylmagnesium bromide (35 mg, 0.292 mmol) was added dropwise and the reaction mixture allowed to warm to RT and stirred for 2 h. Water was added and the reaction mixture extracted into EtOAc (×3). The combined EtOAc layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. Purification by preparative reverse phase HPLC gave the title product (8 mg, 0.023 mmol, 8%).

Workup

temperatureto warm to RT
extractionthe reaction mixture extracted into EtOAc (×3)
washThe combined EtOAc layers were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by preparative reverse phase HPLC

Sources & evidence

ORD record: ord-477d5538e33c47bd923822508605b38c
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129397B2

Reaction notes

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