Borane;tetrahydrofuran → HCID 58169431, compound

HRID 1484918Notes

Reaction equation

HRID 1484918 reaction equation
[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([F:16])=[CH:14][N:13]=[C:12]([C:17]4[S:21][C:20]([C:22](=[O:24])[CH3:23])=[CH:19][CH:18]=4)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1.CB1N2CCC[C@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.B.C1COCC1>C1COCC1>[CH:1]1([C:4]2[NH:8][N:7]=[C:6]([NH:9][C:10]3[C:15]([F:16])=[CH:14][N:13]=[C:12]([C:17]4[S:21][C:20]([C@H:22]([OH:24])[CH3:23])=[CH:19][CH:18]=4)[N:11]=3)[CH:5]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 2723981Borane;tetrahydrofuranHCID 2734713(3aS)-1-methyl-3,3-diphenyl-hexahydropyrrolo(1,2-c)(1,3,2)oxazaboroleHCID 50943609HCID 50943609, compound

Product 1

HCID 58169431HCID 58169431, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of compound 1-(5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoropyrimidin-2-yl)thiophen-2-yl)ethanone (50 mg, 0.15 mmol, 1.0 eq) in dry THF (5 mL) was added dropwise to the mixture of (S)-1-methyl-3,3-diphenyl-hexahydropyrrolo[1,2-c][1,3,2] oxazaborole (0.22 mL, 0.22 mmol, 1.5 eq) and BH3.THF (0.44 mL, 0.44 mmol, 3.0 eq) in dry THF (2 mL) at 0° C. The mixture was stirred for 3 h, quenched with isopropylalcohol and concentrated. The residue was purified by silica gel column chromatography, then, recrystallized with THF/CH2Cl2/Petroleum ether to afford (R)-1-(5-(4-(5-cyclopropyl-1H-pyrazol-3-ylamino)-5-fluoropyrimidin-2-yl)thiophen-2-yl)ethanol (Compound 147) (21 mg, 42%).

Workup

  1. customquenched with isopropylalcohol
  2. concentrationconcentrated
  3. customThe residue was purified by silica gel column chromatography
  4. customrecrystallized with THF/CH2Cl2/Petroleum ether

Sources & evidence

ORD record
ord-b131a114e59949f8a6e421d85b378332
Source dataset
uspto-grants-2016_08
Patent number
US09422271B2

Reaction notes

Loading…