4-Chloropyridine-2-carboxamide → 4-(4-Amino-2-fluorophenoxy)picolinamide

HRID 1670228Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][C:12]([NH:15]C(=O)CC(NC3C=CC(F)=CC=3)=O)=[CH:11][C:10]=2[F:29])[CH:5]=[CH:4][N:3]=1.CC(C)([O-])C.[K+].ClC1C=CN=C([C:43]([NH2:45])=[O:44])C=1>CN(C=O)C>[NH2:15][C:12]1[CH:13]=[CH:14][C:9]([O:8][C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:43]([NH2:45])=[O:44])[CH:7]=2)=[C:10]([F:29])[CH:11]=1

Participants

Conditions

Temperature: 110 °C

Procedure

A solution of 4-amino-2-fluorophenol (Compound A of Example 20, 0.81 g, 6.4 mmol, 1.0 eq) in DMF (6.5 mL) was treated with potassium tert-butoxide (0.79 g, 7.1 mmol, 1.1 eq) at room temperature and the reaction mixture was stirred for 1 h. 4-Chloropicolinamide (1.0 g, 6.4 mmol, 1.0 eq) was added and the reaction mixture was heated to 110° C. for 8 h. The reaction was cooled to room temperature and the reaction mixture quenched with water. The resulting heterogeneous solution was filtered and the solid material was washed with water. The solid was triturated with a small amount of MeOH followed by Et2O. The solid was filtered and dried in vacuo to afford the product (1.3 g, 82%) as a solid. 1H NMR (DMSO-d6) δ 8.49-8.50 (m, 1H), 8.12 (br s, 1H), 7.71 (br s, 1H), 7.35-7.36 (m, 1H), 7.14-7.16 (m, 1H), 7.01-7.06 (m, 1H), 6.44-6.47 (m, 2H), 5.53 (s, 2H); MS (ESI+) m/z 248 (M+H)+.

Workup

temperatureThe reaction was cooled to room temperature
customthe reaction mixture quenched with water
filtrationThe resulting heterogeneous solution was filtered
washthe solid material was washed with water
customThe solid was triturated with a small amount of MeOH
filtrationThe solid was filtered
customdried in vacuo

Sources & evidence

ORD record: ord-a5171a86af63482e8460f7fa91006310
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07989477B2

Reaction notes

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