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

HRID 220575Notes

Reaction equation

[OH:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[Cl:12][C:13]1[C:14]([N:19]2[CH2:24][CH2:23][N:22]([CH2:25][C:26]3[C:27]([CH3:33])=[N:28][N:29]([CH3:32])[C:30]=3[CH3:31])[CH2:21][CH2:20]2)=[N:15][CH:16]=[CH:17][N:18]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.O.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:12].[CH3:32][N:29]1[C:30]([CH3:31])=[C:26]([CH2:25][N:22]2[CH2:21][CH2:20][N:19]([C:14]3[C:13]([C:6]4[CH:7]=[CH:8][C:3]([CH2:2][OH:1])=[CH:4][CH:5]=4)=[N:18][CH:17]=[CH:16][N:15]=3)[CH2:24][CH2:23]2)[C:27]([CH3:33])=[N:28]1

Participants

Conditions

Temperature: 120 °C

Procedure

Stir together 4-(hydroxymethyl)benzeneboronic acid (182 mg, 1.2 mmol), 3′-chloro-4-(1,3,5-trimethyl-1H-pyrazol-4-ylmethyl)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl (321 mg, 1.0 mmol), potassium carbonate (332 mg, 2.4 mmol) and tetrakis(triphenylphosphine)palladium(0) (58 mg, 5 μmol) in dry N,N-dimethylacetamide (4 mL) and water (2 mL) at room temperature. Heat to 120° C. for 6 hr. under nitrogen. Cool to room temperature, purify using SCX chromatography and further purify using silica gel chromatography eluting with (5:95 to 20:80 methanol:DCM). Dissolve in acetonitrile, and add 2 M aq. HCl and water then lyophilize to give the title compound as a peach coloured powder (405 mg, 94%). MS (ES): m/z=393 [M+H].

Workup

temperatureCool to room temperature
custompurify
customfurther purify
washeluting with (5:95 to 20:80 methanol:DCM)
dissolutionDissolve in acetonitrile
additionadd 2 M aq. HCl and water

Sources & evidence

ORD record: ord-3246749354a549198d6a1fc0ed138a28
Source dataset: uspto-grants-2012_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08202873B2

Reaction notes

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