1,2-Diaminocyclohexane, cis- → 6-(cis-2-Amino-cyclohexylamino)-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

HRID 1396339Notes

Reaction equation

HRID 1396339 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]([N:18]3[CH:22]=[CH:21][N:20]=[N:19]3)[N:13]=2)[CH:3]=1.[C@@H:23]1([NH2:30])[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]1[NH2:29]>CN1CCCC1=O.C(=O)(O)[O-].[Na+]>[NH2:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:30][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]([N:18]3[CH:22]=[CH:21][N:20]=[N:19]3)[N:13]=2)[CH:3]=1

Participants

5

Reactant 2

HCID 3429171,2-Diaminocyclohexane, cis-HCID 866897096-Chloro-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

Product 1

HCID 866897106-(cis-2-Amino-cyclohexylamino)-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amideYield 23.7%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
150 °C

Procedure

6-Chloro-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (44 mg, 0.139 mmol) was dissolved in N-methylpyrrolidinone (0.9 mL). cis-Cyclohexane-1,2-diamine (95 mg, 0.834 mmol) was added and the mixture was warmed to 150° C. After 16 h the mixture was cooled and concentrated in vacuo. The residue obtained was diluted with saturated aqueous sodium bicarbonate solution, then extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by chromatography (silica, 0:0:10 to 0.1:1:10 ammonium hydroxide:methanol:dichloromethane) gave 6-(cis-2-amino-cyclohexylamino)-4-(6-[1,2,3]triazol-1-yl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (13 mg, 23%) as a brown solid. 1H NMR (300 MHz, DMSO-d6) δ ppm 10.33 (s, 1H) 9.13 (d, J=8.3 Hz, 1H) 8.84 (d, J=1.1 Hz, 1H) 8.16-8.26 (m, 1H) 8.03 (d, J=0.8 Hz, 1H) 7.96 (d, J=7.9 Hz, 1H) 7.67 (s, 1H) 7.51-7.57 (m, 1H) 7.51-7.57 (m, 1H) 7.43-7.50 (m, 1H) 3.60 (br. s., 1H) 2.96-3.03 (m, 1H) 1.21-1.64 (m, 8H); MS (EI/CI) m/z: 395 [M+H].

Workup

  1. temperatureAfter 16 h the mixture was cooled
  2. concentrationconcentrated in vacuo
  3. customThe residue obtained
  4. extractionextracted with ethyl acetate
  5. washThe combined organic extracts were washed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by chromatography (silica, 0:0:10 to 0.1:1:10 ammonium hydroxide:methanol:dichloromethane)

Sources & evidence

ORD record
ord-b944bc1fc497401d93519e2fbce2744d
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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