Tetrahydrofuran → 3-(3-(5-p-Tolyloxy-thiophen-2-ylmethyl)-isoxazol-5-yl)-pyridin-2,6-diamine

HRID 1691201Notes

Reaction equation

O1CCCC1.[C:6]1([CH3:23])[CH:11]=[CH:10][C:9]([O:12][C:13]2[S:17][C:16]([CH2:18][C:19](Cl)=[N:20][OH:21])=[CH:15][CH:14]=2)=[CH:8][CH:7]=1.[C:24]([C:26]1[C:27]([NH2:33])=[N:28][C:29]([NH2:32])=[CH:30][CH:31]=1)#[CH:25].C(N(CC)CC)C>O>[C:6]1([CH3:23])[CH:11]=[CH:10][C:9]([O:12][C:13]2[S:17][C:16]([CH2:18][C:19]3[CH:25]=[C:24]([C:26]4[C:27]([NH2:33])=[N:28][C:29]([NH2:32])=[CH:30][CH:31]=4)[O:21][N:20]=3)=[CH:15][CH:14]=2)=[CH:8][CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

To a tetrahydrofuran (5.00 mL) solution of (5-p-tolyloxy-thiophen-2-yl)acetohydroximoyl chloride (130 mg, 0.461 mmol) described in Manufacturing Example 48-1-5 and 3-ethynyl-pyridin-2,6-diamine (30.0 mg, 0.226 mmol) described in Manufacturing Example 13-1-3 was added triethylamine (126 μL, 0.903 mmol), which was stirred for 7 hours at 60° C. Water was added to the reaction solution at room temperature, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride and dried over anhydrous magnesium sulfate, and the solvent was evaporated under a reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=2:1) to obtain the title compound (12.0 mg, 14.0%).

Workup

extractionwhich was extracted with ethyl acetate
washThe organic layer was washed with saturated aqueous sodium chloride
dry with materialdried over anhydrous magnesium sulfate
customthe solvent was evaporated under a reduced pressure
customThe residue was purified by NH silica gel column chromatography (ethyl acetate:heptane=2:1)

Sources & evidence

ORD record: ord-a4a9c041c3b1430c88792d766e0235c9
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08153662B2

Reaction notes

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