Hydrochloric Acid → 2-(2-(4-Methylthiazol-2-ylamino)pyridin-4-yloxy)benzonitrile

HRID 910891Notes

Reaction equation

[CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[CH:13]=[C:12]([OH:14])[CH:11]=[CH:10][N:9]=2)[S:5][CH:6]=1.F[C:16]1[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=1[C:18]#[N:19].C(=O)([O-])[O-].[K+].[K+].Cl>CS(C)=O.C1COCC1.CCOCC>[CH3:1][C:2]1[N:3]=[C:4]([NH:7][C:8]2[CH:13]=[C:12]([O:14][C:16]3[CH:23]=[CH:22][CH:21]=[CH:20][C:17]=3[C:18]#[N:19])[CH:11]=[CH:10][N:9]=2)[S:5][CH:6]=1

Participants

Conditions

Temperature: 90 °C

Procedure

2-(4-Methylthiazol-2-ylamino)pyridin-4-ol (0.100 g, 0.483 mmol), 2-fluorobenzonitrile (0.064 g, 0.531-mmol) and potassium carbonate (0.167 g, 1.21 mmol) were combined in DMSO and heated at 90° C. overnight. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed with water and brine, dried, and concentrated. The residue was purified by MPLC, eluting with 3:1 hexane:ethyl acetate to afford the free base. The free base was dissolved in THF (3 mL) and 1M HCl in ether (6 mL) was added. The solution was diluted with ether (15 mL), triturated for 10 minutes, and filtered to afford 2-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzonitrile (0.013 g, 8.65% yield) as white solid. 1H NMR (CDCl3) δ 8.26 (d, 1H), 7.72 (dd, 1H), 7.60 (m, 1H), 7.32 (dt, 1H), 7.14 (d, 1H), 6.53 (dd, 1H), 6.42 (d, 1H), 6.33 (d, 1H), 2.23 (d, 3H); HPLC Rt=2.67 min; Mass spectrum (esi) m/z=309 (M+H).

Workup

customThe reaction mixture was partitioned between ethyl acetate and water
washThe organic layer was washed with water and brine
customdried
concentrationconcentrated
customThe residue was purified by MPLC
washeluting with 3:1 hexane
customethyl acetate to afford the free base
customtriturated for 10 minutes
filtrationfiltered

Sources & evidence

ORD record: ord-ac89c7fcb86b4bd2af59eaa0083cf9b6
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022222B2

Reaction notes

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