5-Fluoro-6-methylpyridin-2-amine → Ethyl 6-chloro-4-(5-fluoro-6-methylpyridin-2-ylamino)pyridazine-3-carboxylate

HRID 1396374Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[N:4][C:3]=1[C:9]([O:11][CH2:12][CH3:13])=[O:10].[F:14][C:15]1[CH:16]=[CH:17][C:18]([NH2:22])=[N:19][C:20]=1[CH3:21]>C(#N)C>[Cl:8][C:6]1[N:5]=[N:4][C:3]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:2]([NH:22][C:18]2[CH:17]=[CH:16][C:15]([F:14])=[C:20]([CH3:21])[N:19]=2)[CH:7]=1

Participants

Conditions

Temperature: 140 °C

Procedure

A pressure tube was charged with ethyl 4,6-dichloropyridazine-3-carboxylate (300 mg, 1.36 mmol), 5-fluoro-6-methylpyridin-2-amine (257 mg, 2.04 mmol), and acetonitrile (8 mL) and then heated at 140° C. for 3 d. After cooling to room temperature the reaction mixture was concentrated in vacuo and the residue purified by chromatography (silica, 50 μm, 80 g, Analogix, 0 to 10% acetone in dichloromethane, 25 min) to afford ethyl 6-chloro-4-(5-fluoro-6-methylpyridin-2-ylamino)pyridazine-3-carboxylate (69 mg, 16%) as a yellow solid. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 10.72 (br. s., 1H) 9.06 (s, 1H) 7.38 (s, 1H) 6.74-6.85 (m, 1H) 4.58 (q, J=7.07 Hz, 2H) 2.56 (d, J=3.03 Hz, 3H) 1.53 (t, J=7.07 Hz, 3H) 1.27 (s, 1H). LCMS (EI/CI) m/z: 311 [M+H].

Workup

temperatureAfter cooling to room temperature the reaction mixture
concentrationwas concentrated in vacuo
customthe residue purified by chromatography (silica, 50 μm, 80 g, Analogix, 0 to 10% acetone in dichloromethane, 25 min)

Sources & evidence

ORD record: ord-f9fc7037b62a41eba07f8bebf56c3022
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901124B2

Reaction notes

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