(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4,6-dimethylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396394Notes

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]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[N:13]=2)[CH:3]=1.[NH2:20][C@@H:21]1[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]1[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:33])([CH3:32])[CH3:31]>CN1C(=O)CCC1.C(OCC)(=O)C.[Cl-].[Na+].O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:20][C@@H:21]2[CH2:26][CH2:25][CH2:24][CH2:23][C@@H:22]2[NH:27][C:28](=[O:34])[O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH3:19])[N:13]=1)(=[O:9])[NH2:10]

Participants

Conditions

Temperature: 130 °C

Procedure

To a solution of 6-chloro-4-(4,6-dimethylpyridin-2-ylamino)pyridazine-3-carboxamide (140 mg, 504 μmol) in NMP (2.52 mL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (216 mg, 1.01 mmol) and the mixture heated at 130° C. for 72 h. The reaction mixture was cooled and diluted with ethyl acetate and brine. The organic phase was washed with brine (2×) and water (1×), then the organic phase was concentrated in vacuo then purified by chromatography (silica, 40-100% ethyl acetate in hexanes) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(4,6-dimethylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (75 mg, 98.8 μmol, 20%) as an orange solid. MS (EI/CI) m/z: 456.2 [M+H].

Workup

temperatureThe reaction mixture was cooled
washThe organic phase was washed with brine (2×) and water (1×)
concentrationthe organic phase was concentrated in vacuo
customthen purified by chromatography (silica, 40-100% ethyl acetate in hexanes)

Sources & evidence

ORD record: ord-7349bd9a7f8e4b42b3064c6289cba1d9
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08901124B2

Reaction notes

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