Thiazole → 6-(3-Fluorophenyl)-5-(1,3-thiazol-5-yl)pyrazin-2-amine

HRID 1710693Notes

Reaction equation

Br[C:2]1[N:3]=[CH:4][C:5]([NH2:15])=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([F:14])[CH:9]=1.[S:16]1[CH:20]=[CH:19][N:18]=[CH:17]1.C([O-])(=O)C.[K+]>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>[F:14][C:10]1[CH:9]=[C:8]([C:7]2[N:6]=[C:5]([NH2:15])[CH:4]=[N:3][C:2]=2[C:20]2[S:16][CH:17]=[N:18][CH:19]=2)[CH:13]=[CH:12][CH:11]=1

Participants

Conditions

Temperature: 150 °C

Procedure

A mixture of 5-bromo-6-(3-fluorophenyl)pyrazin-2-amine (Preparation 1, 100 mg, 0.37 mmol), thiazole (0.06 mL, 0.88 mmol) and potassium acetate (54 mg, 0.56 mmol) in N,N-dimethylacetamide (1 mL) was degassed with argon. The catalyst Pd(PPh3)4 (23 mg, 0.02 mmol, 5 mol %) was added and degassing was repeated. The mixture was heated to 150° C. in a sealed tube and stirred overnight. The mixture was cooled and ethyl acetate and aqueous NH4Cl were added. The aqueous layer was extracted with ethyl acetate. The organic layer was dried and concentrated. The residue was purified by flash silica gel chromatography (hexanes/EtOAc 1:1) to give the title compound (15 mg, 15%) as a yellow solid.

Workup

customwas degassed with argon
customdegassing
temperatureThe mixture was cooled
additionethyl acetate and aqueous NH4Cl were added
extractionThe aqueous layer was extracted with ethyl acetate
customThe organic layer was dried
concentrationconcentrated
customThe residue was purified by flash silica gel chromatography (hexanes/EtOAc 1:1)

Sources & evidence

ORD record: ord-3b4e63fdc40a4595a055f67b308f0ab7
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07790728B2

Reaction notes

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