Water → {2-Fluoro-4-[4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenyl}-methanol hydrochloride

HRID 220576Notes

Reaction equation

HRID 220576 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:13][CH2:12][N:11]([CH2:14][C:15]3[CH:16]=[N:17][N:18]([C:21]4[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=4)[C:19]=3[CH3:20])[CH2:10][CH2:9]2)=[N:4][CH:5]=[CH:6][N:7]=1.[F:27][C:28]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[CH:30][C:29]=1[CH2:43][OH:44].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[ClH:1].[F:27][C:28]1[CH:33]=[C:32]([C:2]2[C:3]([N:8]3[CH2:13][CH2:12][N:11]([CH2:14][C:15]4[CH:16]=[N:17][N:18]([C:21]5[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=5)[C:19]=4[CH3:20])[CH2:10][CH2:9]3)=[N:4][CH:5]=[CH:6][N:7]=2)[CH:31]=[CH:30][C:29]=1[CH2:43][OH:44]

Participants

7

Reactant 4

HCID 962Water2×HCID 11430Potassium CarbonateHCID 59535334(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)methanolHCID 866416633'-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl

Product 1

HCID 68594485{2-Fluoro-4-[4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-3'-yl]-phenyl}-methanol hydrochlorideYield 82%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 31374DimethylacetamideSolvent

Procedure

Stir together 3′-chloro-4-(5-methyl-1-phenyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (184 mg, 0.50 mmol), [2-fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanol (151 mg, 0.60 mmol), potassium carbonate (166 mg, 1.20 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.006 g, 0.003 mmol) and water (1 mL), in N,N-dimethylacetamide (2 mL) at room temperature under nitrogen, then heat at 120° C. for 3 hr. Cool to room temperature, add water (20 mL) and extract with DCM (3×20 mL). Pass the combined DCM extracts through an IST Phase Separator Frit®, concentrate and purify (silica gel chromatography, eluting with 5:95 to 15:85 methanol:DCM). Dry in a vacuum oven over night, then dissolve the yellow powder in acetonitrile. Add 2 M aq. HCl and water then lyophilize to give the title compound as light yellow powder (203 mg, 82%). MS (ES): m/z=459 [M+H].

Workup

  1. extractionextract with DCM (3×20 mL)
  2. concentrationconcentrate
  3. custompurify
  4. wash(silica gel chromatography, eluting with 5:95 to 15:85 methanol:DCM)
  5. customDry in a vacuum oven over night
  6. dissolutiondissolve the yellow powder in acetonitrile
  7. additionAdd 2 M aq. HCl and water

Sources & evidence

ORD record
ord-bbac01254a4b459d9179cfe5d7f6d173
Source dataset
uspto-grants-2012_06
Patent number
US08202873B2

Reaction notes

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