Hydrochloric Acid → 6-Methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine

HRID 2278991Notes

Reaction equation

[CH3:1][C:2]1[N:7]=[C:6]([NH:8]C(=O)C)[CH:5]=[CH:4][C:3]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([C:19]2[O:23][N:22]=[C:21]([CH3:24])[CH:20]=2)[CH:14]=1.Cl.CCOC(C)=O.C([O-])(O)=O.[Na+]>C1COCC1.O>[CH3:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][C:3]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([C:19]2[O:23][N:22]=[C:21]([CH3:24])[CH:20]=2)[CH:14]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A mixture of N-(6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-yl)acetamide (0.11 g, 0.339 mmol) and 2M HCl (1.696 mL, 3.39 mmol) in THF (3 mL) was heated at 60° C. for 4 h. The mixture was cooled to RT, treated with EtOAc and H2O, neutralized with NaHCO3, the layers separated and the aqueous layer extracted with EtOAc (1×). The combined organics were washed with brine, dried over Na2SO4 and concentrated to dryness to afford 6-methyl-5-((2-(3-methylisoxazol-5-yl)pyridin-4-yl)oxy)pyridin-2-amine (90 mg, 94%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 8.51 (d, J=5.7 Hz, 1 H); 7.26 (d, J=2.5 Hz, 1 H); 7.22 (d, J=8.7 Hz, 1 H); 6.95 (s, 1 H); 6.89 (dd, J=5.7, 2.5 Hz, 1 H); 6.36 (d, J=8.7 Hz, 1 H); 6.00 (s, 2 H); 2.28 (s, 3 H); 2.06 (s, 3 H); MS (ESI) m/z: 283.1 (M+H+).

Workup

temperatureThe mixture was cooled to RT
customthe layers separated
extractionthe aqueous layer extracted with EtOAc (1×)
washThe combined organics were washed with brine
dry with materialdried over Na2SO4
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-4aef9a8242374989b1354af9f965db15
Source dataset: uspto-grants-2015_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09133183B2

Reaction notes

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