Boron trifluoride etherate → 5-[4-Fluoro-3-(morpholinomethyl)phenyl]-3-(1-isopropyltriazol-4-yl)pyridin-2-amine

HRID 1053137Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:9]=[CH:10][C:11]([F:22])=[C:12]([C:14]([N:16]3[CH2:21][CH2:20][O:19][CH2:18][CH2:17]3)=O)[CH:13]=2)=[CH:4][C:3]=1[C:23]1[N:24]=[N:25][N:26]([CH:28]([CH3:30])[CH3:29])[CH:27]=1.B(F)(F)F.CCOCC.[BH4-].[Na+]>C1COCC1>[F:22][C:11]1[CH:10]=[CH:9][C:8]([C:5]2[CH:4]=[C:3]([C:23]3[N:24]=[N:25][N:26]([CH:28]([CH3:29])[CH3:30])[CH:27]=3)[C:2]([NH2:1])=[N:7][CH:6]=2)=[CH:13][C:12]=1[CH2:14][N:16]1[CH2:17][CH2:18][O:19][CH2:20][CH2:21]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of [5-[6-amino-5-(1-isopropyltriazol-4-yl)-3-pyridyl]-2-fluoro-phenyl]-morpholino-methanone (150 mg, 0.365 mmol) in THF (10.0 mL) was added BF3.Et2O (0.25 mL, 1.827 mmol) at 0° C. and stirred for 30 min. After 30 min, NaBH4 (69 mg, 1.827 mmol) was added at 0° C. and stirred at room temperature for 18 h. After cooling to 0° C., quenched with MeOH (2 mL) and heated to reflux for 6 h. The reaction mixture was diluted with EtOAc (20 mL), washed with water (20 mL), dried over anhydrous Na2SO4 and solvent was evaporated under reduced pressure. Crude compound was purified by column using 100-200 mesh silica gel. The column was eluted with 5% MeOH in DCM to afford 60 mg (yield: 41.66%) of the title compound as white solid.

Workup

waitAfter 30 min
stirringstirred at room temperature for 18 h
customquenched with MeOH (2 mL)
temperatureheated
temperatureto reflux for 6 h
additionThe reaction mixture was diluted with EtOAc (20 mL)
washwashed with water (20 mL)
dry with materialdried over anhydrous Na2SO4 and solvent
customwas evaporated under reduced pressure
customCrude compound was purified by column
washThe column was eluted with 5% MeOH in DCM

Sources & evidence

ORD record: ord-3468793a45514c0bb69c1ed0becfbbc6
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09393248B1

Reaction notes

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