Potassium Hydroxide → HCID 77844977, compound

HRID 1519156Notes

Reaction equation

HRID 1519156 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5]([C:8]2[C:9]([F:19])=[C:10]([OH:18])[C:11]([CH:14]3[CH2:17][CH2:16][CH2:15]3)=[CH:12][CH:13]=2)=[N:6][CH:7]=1.Br[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=1.[OH-].[K+]>CS(C)=O>[CH:14]1([C:11]2[CH:12]=[CH:13][C:8]([C:5]3[N:6]=[CH:7][C:2]([NH2:1])=[N:3][CH:4]=3)=[C:9]([F:19])[C:10]=2[O:18][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][CH:23]=2)[CH2:15][CH2:16][CH2:17]1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 680214-Fluorobenzyl bromideHCID 90311095HCID 90311095, compound

Product 1

HCID 77844977HCID 77844977, compoundYield 53%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a solution of 3-(5-aminopyrazin-2-yl)-6-cyclobutyl-2-fluorophenol (50 mg, 0.19 mmol) and 1-(bromomethyl)-4-fluorobenzene (36 μL, 0.29 mmol) in DMSO (1 mL) was added 1 pellet (˜125 mg) of potassium hydroxide. The reaction was stirred for 16 hours at room temperature before filtering and purifying by HPLC to give 5-{4-cyclobutyl-2-fluoro-3-[(4-fluorobenzyl)oxy]phenyl}pyrazin-2-amine (37 mg, 39%). MS (ESI): mass calcd. for C21H19F2N3O, 367.15; m/z found, 368.1 [M+H]+. 1H NMR (400 MHz, CD3OD) δ 8.30 (d, J=1.3, 1H), 8.22 (s, 1H), 7.58 (m, 1H), 7.50-7.43 (m, 2H), 7.20 (d, J=8.0, 1H), 7.15-7.07 (m, 2H), 5.01 (s, 2H), 3.83-3.68 (m, 1H), 2.31-2.21 (m, 2H), 2.18-1.93 (m, 3H), 1.87-1.78 (m, 1H).

Workup

  1. filtrationbefore filtering
  2. custompurifying by HPLC

Sources & evidence

ORD record
ord-eeafd683b58041fba32d3a2aedbc6eea
Source dataset
uspto-grants-2015_07
Patent number
US09073876B2

Reaction notes

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