Diisopropylethylamine → {(1S,2R)-2-[6-carbamoyl-5-(6-methyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 1396358Notes

Reaction equation

HRID 1396358 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]([CH3:18])[N:13]=2)[CH:3]=1.C(N(CC)C(C)C)(C)C.[NH2:28][C@@H:29]1[CH2:34][CH2:33][CH2:32][CH2:31][C@@H:30]1[NH:35][C:36](=[O:42])[O:37][C:38]([CH3:41])([CH3:40])[CH3:39]>CN1CCCC1=O>[C:38]([O:37][C:36](=[O:42])[NH:35][C@H:30]1[CH2:31][CH2:32][CH2:33][CH2:34][C@H:29]1[NH:28][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]([CH3:18])[N:13]=2)[CH:3]=1)([CH3:41])([CH3:39])[CH3:40]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 866897076-Chloro-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide

Product 1

HCID 86689725{(1S,2R)-2-[6-carbamoyl-5-(6-methyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl esterYield 36.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

6-Chloro-4-(6-methyl-pyridin-2-ylamino)-pyridazine-3-carboxylic acid amide (130 mg, 0.49 mmol), N,N-diisopropylethylamine (0.17 mL, 0.986 mmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (211 mg, 0.986 mmol) were dissolved in N-methylpyrrolidinone (2 mL) and heated at 150° C. for 2 d. 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-methyl-pyridin-2-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (78 mg, 35%) as a light brown amorphous residue. LCMS (EI/CI) m/z: 442 [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-9aef6cd0c0ca4baa8f93d41293f5fd3c
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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