Cyclohexylamine → 6-(Cyclohexylamino)-4-(6-cyclopropylpyridin-2-ylamino)pyridazine-3-carboxamide

HRID 1396400Notes

Reaction equation

Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]3[CH2:20][CH2:19]3)[N:13]=2)[CH:3]=1.[CH:21]1([NH2:27])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1>CN1CCCC1=O>[CH:21]1([NH:27][C:2]2[N:7]=[N:6][C:5]([C:8]([NH2:10])=[O:9])=[C:4]([NH:11][C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]4[CH2:20][CH2:19]4)[N:13]=3)[CH:3]=2)[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

Conditions

Temperature: 130 °C

Procedure

A suspension of 6-chloro-4-(6-cyclopropylpyridin-2-ylamino)pyridazine-3-carboxamide (100 mg, 345 μmol, prepared as described for example 12) and cyclohexylamine (342 mg, 395 μL, 3.45 mmol) in N-methyl-2-pyrrolidinone (0.5 mL) was heated at 130° C. for 14 h. The mixture was cooled and concentrated under high vacuum at 120° C. to remove all residual solvent and amine starting material. The brown solid obtained was purified by chromatography (silica, 11 g spherical, 0-20% acetone in dichloromethane, 20 min) to give 6-(cyclohexylamino)-4-(6-cyclopropylpyridin-2-ylamino)pyridazine-3-carboxamide (81 mg, 230 μmol, 67% yield) as a white solid. 1H NMR (DMSO-d6) δ: 11.72 (br. s., 1H), 8.37 (br. s., 1H), 7.83 (s, 1H), 7.62 (br. s., 1H), 7.56 (t, J=7.7 Hz, 1H), 7.10 (d, J=7.8 Hz, 1H), 6.88 (d, J=7.3 Hz, 1H), 6.66 (d, J=8.1 Hz, 1H), 3.52-3.69 (m, 1H), 2.04-2.18 (m, 1H), 1.90-2.00 (m, 2H), 1.72-1.82 (m, 2H), 1.63 (d, J=12.6 Hz, 1H), 1.24-1.45 (m, 4H), 1.09-1.23 (m, 1H), 0.95-1.03 (m, 4H); MS (EI/CI) m/z: 353.1 [M+H].

Workup

temperatureThe mixture was cooled
concentrationconcentrated under high vacuum at 120° C.
customto remove all residual solvent and amine starting material
customThe brown solid obtained
customwas purified by chromatography (silica, 11 g spherical, 0-20% acetone in dichloromethane, 20 min)

Sources & evidence

ORD record: ord-8ae96684c3fb40c28d7ef8fdb6587256
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901124B2

Reaction notes

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