(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → tert-butyl (1S,2R)-2-(5-(6-(2H-1,2,3-triazol-2-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate

HRID 1396411Notes

Reaction equation

HRID 1396411 reaction equation
[N:1]1[N:2]([C:6]2[N:11]=[C:10]([NH:12][C:13]3[CH:18]=[C:17](Cl)[N:16]=[N:15][C:14]=3[C:20]([NH2:22])=[O:21])[CH:9]=[CH:8][CH:7]=2)[N:3]=[CH:4][CH:5]=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>[N:1]1[N:2]([C:6]2[N:11]=[C:10]([NH:12][C:13]3[CH:18]=[C:17]([NH:23][C@@H:24]4[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]4[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])[N:16]=[N:15][C:14]=3[C:20](=[O:21])[NH2:22])[CH:9]=[CH:8][CH:7]=2)[N:3]=[CH:4][CH:5]=1

Participants

6

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2×HCID 866897614-(6-(2H-1,2,3-triazol-2-yl)pyridin-2-ylamino)-6-chloropyridazine-3-carboxamide

Product 1

HCID 86689762tert-butyl (1S,2R)-2-(5-(6-(2H-1,2,3-triazol-2-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamateYield 56.3%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
140 °C

Procedure

To a solution of 4-(6-(2H-1,2,3-triazol-2-yl)pyridin-2-ylamino)-6-chloropyridazine-3-carboxamide (90 mg, 284 μmol) in NMP (947 μL) was added tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (122 mg, 568 μmol) and the mixture heated to 140° C. for 16 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (61 mg, 284 μmol) was added and the mixture heated for a further 16 h. The reaction mixture was cooled, diluted with ethyl acetate and brine, then the phases were separated and the organic phase collected and washed with brine (2×). The organic layer was concentrated in vacuo then purified by chromatography (silica, 2-5% methanol in dichloromethane) to give a residue that was triturated with ethyl acetate, filtered, and washed with ether to give tert-butyl (1S,2R)-2-(5-(6-(2H-1,2,3-triazol-2-yl)pyridin-2-ylamino)-6-carbamoylpyridazin-3-ylamino)cyclohexylcarbamate (79 mg, 160 μmol, 56%) as a brown solid. MS (EI/CI) m/z: 495.1 [M+H].

Workup

  1. temperaturethe mixture heated for a further 16 h
  2. temperatureThe reaction mixture was cooled
  3. customthe phases were separated
  4. customthe organic phase collected
  5. washwashed with brine (2×)
  6. concentrationThe organic layer was concentrated in vacuo
  7. customthen purified by chromatography (silica, 2-5% methanol in dichloromethane)
  8. customto give a residue that
  9. customwas triturated with ethyl acetate
  10. filtrationfiltered
  11. washwashed with ether

Sources & evidence

ORD record
ord-d8805c81bf8d49649574a807a2d57f4f
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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