Methoxytrimethylsilane → 6-((1R,2S)-2-amino-cyclohexylamino)-4-(5,6-dimethoxy-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

HRID 1396391Notes

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][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[N:13]=2)[CH:3]=1.[NH2:22][C@@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH:29]C(=O)OC(C)(C)C.CO[Si](C)(C)C>CN1C(=O)CCC1>[NH2:22][C@H:23]1[CH2:28][CH2:27][CH2:26][CH2:25][C@H:24]1[NH:29][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][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[N:13]=2)[CH:3]=1

Participants

Conditions

Temperature: 150 °C

Procedure

To 6-chloro-4-(5,6-dimethoxypyridin-2-ylamino)pyridazine-3-carboxamide (500 mg, 1.6 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (692 mg, 3.2 mmol) in NMP (1.5 mL), methoxy trimethylsilane (0.5 mL, 3.6 mmol) was added and the mixture heated to 150° C. for 65 h. The mixture was concentrated under high vacuum to obtain a sticky crude mass that was purified by chromatography (silica, 100-200 mesh, 1-10% methanol in dichloromethane) to give 6-((1R,2S)-2-amino-cyclohexylamino)-4-(5,6-dimethoxy-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (220 mg 35%) as a yellow solid. LC-MS 388 [M+H]+.

Workup

concentrationThe mixture was concentrated under high vacuum
customto obtain a sticky crude mass that
customwas purified by chromatography (silica, 100-200 mesh, 1-10% methanol in dichloromethane)

Sources & evidence

ORD record: ord-17738304fb05476ab3adc0b706c23573
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901124B2

Reaction notes

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