(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689740, compound

HRID 1396378Notes

Reaction equation

HRID 1396378 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][CH:15]=[C:14]([CH2:18][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]>CN1CCCC1=O>[C:30]([O:29][C:28](=[O:34])[NH:27][C@H:22]1[CH2:23][CH2:24][CH2:25][CH2:26][C@H:21]1[NH:20][C:2]1[N:7]=[N:6][C:5]([C:8](=[O:9])[NH2:10])=[C:4]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([CH2:18][CH3:19])[N:13]=2)[CH:3]=1)([CH3:33])([CH3:31])[CH3:32]

Participants

4

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2×HCID 86689739HCID 86689739, compound

Product 1

HCID 86689740HCID 86689740, compoundYield 46.7%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

6-Chloro-4-(6-ethyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (218 mg, 0.785 mmol), and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (336 mg, 1.57 mmol) were dissolved in N-methylpyrrolidinone (4 mL) and heated at 150° C. for 40 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (168 mg, 0.78 mmol) was added and the heating continued for 16 h more. The reaction mixture was cooled and concentrated in vacuo, then diluted with water, and extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (sodium sulfate), filtered and concentrated in vacuo. Purification by chromatography (silica, 0 to 5% methanol in dichloromethane) gave {(1S,2R)-2-[6-carbamoyl-5-(6-ethyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (167 mg, 46%) as a light brown amorphous residue. 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 11.44 (s, 1H) 8.47 (s, 1H) 7.97-8.03 (m, 1H) 7.52 (t, J=7.6 Hz, 1H) 7.22-7.26 (m, 1H) 6.78 (d, J=7.2 Hz, 1H) 6.70 (d, J=7.9 Hz, 1H) 5.38-5.43 (m, 1H) 4.92-5.00 (m, 1H) 3.97-4.08 (m, 2H) 2.80 (q, J=7.6 Hz, 2H) 1.58-1.96 (m, 8H) 1.41 (s, 9H) 1.31-1.39 (m, 3H); LCMS (EI/CI) m/z: 456 [M+H].

Workup

  1. temperatureThe reaction mixture was cooled
  2. concentrationconcentrated in vacuo
  3. additiondiluted with water
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with brine
  6. dry with materialdried (sodium sulfate)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by chromatography (silica, 0 to 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-cf8fcddcc54449e4b475d6b50155bcf7
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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