(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689792, compound

HRID 1396453Notes

Reaction equation

HRID 1396453 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]([CH:19]([CH3:21])[CH3:20])[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:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33]>CN1C(=O)CCC1.C(OCC)(=O)C.O>[C:8]([C:5]1[N:6]=[N:7][C:2]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[C:16]([CH3:18])[CH:15]=[C:14]([CH:19]([CH3:21])[CH3:20])[N:13]=1)(=[O:9])[NH2:10]

Participants

6

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689791HCID 86689791, compound

Product 1

HCID 86689792HCID 86689792, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
140 °C

Procedure

To a stirred solution of 6-chloro-4-(6-isopropyl-4-methylpyridin-2-ylamino)pyridazine-3-carboxamide (54 mg, 177 μmol) in NMP (590 μL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (227.1 mg, 883 μmol) in three portions approximately every 12 h and while heating the mixture (in the periods between additions) at 140° C. After a total of 36 h, the mixture was cooled and then diluted with ethyl acetate and water. The organic phase was separated and then washed with water and brine. The organic phase was then concentrated in vacuo and finally purified by chromatography (silica, 30 to 80% ethyl acetate in hexanes) to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-isopropyl-4-methylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (35 mg, 72.4 μmol, 41.0%) as a brown oil. MS (EI/CI) m/z: 484.3 [M+H].

Workup

  1. temperatureAfter a total of 36 h, the mixture was cooled
  2. customThe organic phase was separated
  3. washwashed with water and brine
  4. concentrationThe organic phase was then concentrated in vacuo
  5. customfinally purified by chromatography (silica, 30 to 80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-aab4979f41994ca4934dbea93a5437ff
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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