(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689785, compound

HRID 1396442Notes

Reaction equation

HRID 1396442 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]([CH:20]([CH3:22])[CH3:21])[N:13]=2)[CH:3]=1.[NH2:23][C@@H:24]1[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]1[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:36])([CH3:35])[CH3:34]>CN1C(=O)CCC1.C(OCC)(=O)C.[Cl-].[Na+].O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([CH:20]([CH3:22])[CH3:21])[N:13]=1)(=[O:9])[NH2:10]

Participants

6

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 89675036HCID 89675036, compound

Product 1

HCID 86689785HCID 86689785, compoundYield 32.4%

Reagents, catalysts & solvents 3

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6-chloro-4-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazine-3-carboxamide (199 mg, 618 μmol) in NMP (2.06 mL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (532 mg, 2.47 mmol) in four portions approximately every 12 h while heating at 140° C. After a total heating time of 48 h, the mixture was cooled, diluted with ethyl acetate and brine, then the phases were separated and the organic phase washed twice more with brine. The organic phase was concentrated in vacuo then purified by chromatography (silica, 1 to 5% methanol in dichloromethane) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-isopropyl-5-methoxypyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (100 mg, 200 μmol, 32%) as a brown solid. MS (EI/CI) m/z: 500.4 [M+H].

Workup

  1. temperatureAfter a total heating time of 48 h, the mixture was cooled
  2. customthe phases were separated
  3. washthe organic phase washed twice more with brine
  4. concentrationThe organic phase was concentrated in vacuo
  5. customthen purified by chromatography (silica, 1 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-901f8ac5737348da9b980e87f029ef67
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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