Potassium Phosphate, Tribasic → (2'-(Trifluoromethyl)-2,4'-bipyridin-5-yl)methanamine

HRID 711254Notes

Reaction equation

Cl.Cl[C:3]1[N:8]=[CH:7][C:6]([CH2:9][NH2:10])=[CH:5][C:4]=1C.[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[C:18](B(O)O)[CH:17]=[CH:16][N:15]=1.COC1C=CC=C(OC)C=1C1C=CC=CC=1P(C1CCCCC1)C1CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CC([O-])=O.CC([O-])=O.[Pd+2].CC(O)CC>[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[C:18]([C:3]2[CH:4]=[CH:5][C:6]([CH2:9][NH2:10])=[CH:7][N:8]=2)[CH:17]=[CH:16][N:15]=1

Participants

Conditions

Temperature: 100 °C

Procedure

To a flask containing (6-chloro-5-methylpyridin-3-yl)methanamine 30-4 (500 mg, 2.20 mmol), 2-(trifluoromethyl)pyridin-4-ylboronic acid 33-1 (418 mg, 2.20 mmol), Pd(OAc)2 (29 mg, 0.11 mmol), S-Phos (91 mg, 0.22 mmol) and potassium phosphate (1.40 g, 6.60 mmol) under Argon was added 2-butanol (4 mL). The mixture was stirred at 100° C. for 10 hours. After cooling to room temperature, the mixture was filtered through celite cake. The filtrate was diluted with ethyl acetate, washed with H2O and brine, dried over Na2SO4, and concentrated to dryness by rotary evaporation. The crude product was purified by silica gel flash chromatography, and eluted with 5% methanol containing ˜7N ammonia in dichloromethane to give (2′-(trifluoromethyl)-2,4′-bipyridin-5-yl)methanamine 48-1 as a dark yellow solid. MS m/z 268.1 (M+1)

Workup

temperatureAfter cooling to room temperature
filtrationthe mixture was filtered through celite cake
additionThe filtrate was diluted with ethyl acetate
washwashed with H2O and brine
dry with materialdried over Na2SO4
concentrationconcentrated to dryness by rotary evaporation
customThe crude product was purified by silica gel flash chromatography
washeluted with 5% methanol containing ˜7N ammonia in dichloromethane

Sources & evidence

ORD record: ord-5f65d11c70b841fc8e89cd250e4370ec
Source dataset: uspto-grants-2015_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09181235B2

Reaction notes

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