Tetrahydrofuran → 1-[4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl]-2-methylpropan-2-ol

HRID 410706Notes

Reaction equation

[CH3:1][C:2]([OH:19])([CH3:18])[CH2:3][N:4]1[CH:8]=[C:7](B2OC(C)(C)C(C)(C)O2)[CH:6]=[N:5]1.[Cl:20][C:21]1[N:26]=[C:25](Cl)[CH:24]=[CH:23][N:22]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C1COCC1>O>[Cl:20][C:21]1[N:26]=[C:25]([C:7]2[CH:6]=[N:5][N:4]([CH2:3][C:2]([CH3:1])([OH:19])[CH3:18])[CH:8]=2)[CH:24]=[CH:23][N:22]=1

Participants

Conditions

Temperature: 120 °C

Procedure

To a mixture of the product from Step 1 (84 mg, 0.31 mmol), 2,4-dichloropyrimidine (47 mg, 0.31 mmol), potassium phosphate, tribasic (167 mg, 0.79 mmol), and 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (26 mg, 0.031 mmol) was added THF (2 mL) and water (0.2 mL). The mixture was heated to 120° C. for 15 minutes under microwave irradiation, cooled to room temperature, quenched with 1:1 water:brine, and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, and concentrated. Purification by column chromatography on silica gel (Biotage 10 G, eluting with 0:100 to 100:0 ethyl acetate:hexanes) afforded 1-[4-(2-chloropyrimidin-4-yl)-1H-pyrazol-1-yl]-2-methylpropan-2-ol (44 mg, 0.18 mmol, 56% yield) as a yellow solid. MS ESI: [M+H]+ m/z 253.0.

Workup

temperaturecooled to room temperature
customquenched with 1:1 water
extractionbrine, and extracted with ethyl acetate
dry with materialThe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated
customPurification by column chromatography on silica gel (Biotage 10 G, eluting with 0:100 to 100:0 ethyl acetate:hexanes)

Sources & evidence

ORD record: ord-945f65ead96b4a849d9c48ef5e7074b5
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08759366B2

Reaction notes

Loading…