Ethyl 4,6-dichloropyridazine-3-carboxylate → 3-Pyridazinecarboxylic acid, 6-chloro-4-[[6-(1-cyano-1-methylethyl)-2-pyridinyl]amino]-, ethyl ester

HRID 1396457Notes

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].[NH2:14][C:15]1[N:20]=[C:19]([C:21]([CH3:25])([CH3:24])[C:22]#[N:23])[CH:18]=[CH:17][CH:16]=1>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:14][C:15]2[CH:16]=[CH:17][CH:18]=[C:19]([C:21]([C:22]#[N:23])([CH3:25])[CH3:24])[N:20]=2)[CH:7]=1

Participants

Conditions

Temperature: 130 °C

Procedure

A mixture of ethyl 4,6-dichloropyridazine-3-carboxylate (1.4 g, 6.33 mmol) and 2-(6-aminopyridin-2-yl)-2-methylpropanenitrile (2.04 g, 12.7 mmol) was dissolved in acetonitrile (3.00 mL) and heated to 130° C. for 18 h. The mixture was cooled, concentrated, the residue was adsorbed on silica gel and purified by flash chromatography (silica gel 45 μM, 160 g, Thomson) eluting with 0 to 20% acetone in dichloromethane over 20 min, impure desired product was isolated, all fractions containing desired product were concentrated and the residue dissolved in a dichloromethane and evaporated to a small volume where a solid precipitated, filtered and dried and corresponded to the desired ethyl 6-chloro-4-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxylate (792 mg, 36.2% yield). 1H NMR (CHLOROFORM-d) δ: 10.86 (s, 1H), 9.27 (s, 1H), 7.75 (t, J=7.9 Hz, 1H), 7.26 (d, J=7.9 Hz, 1H), 6.90 (d, J=7.9 Hz, 1H), 4.58 (q, J=7.2 Hz, 2H), 1.81 (s, 6H), 1.52 (t, J=7.2 Hz, 3H); LC-MS 346.1 [M+H]+.

Workup

temperatureThe mixture was cooled
concentrationconcentrated
custompurified by flash chromatography (silica gel 45 μM, 160 g, Thomson)
washeluting with 0 to 20% acetone in dichloromethane over 20 min

Sources & evidence

ORD record: ord-cc17bae2e6504504b8dfdceb71e14db0
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901124B2

Reaction notes

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