(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → {(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester

HRID 1396368Notes

Reaction equation

HRID 1396368 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[N:17]=[C:16]3[N:18]([CH3:21])[CH:19]=[CH:20][C:15]3=[CH:14][CH: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]>CN1CCCC1=O>[C:32]([O:31][C:30](=[O:36])[NH:29][C@H:24]1[CH2:25][CH2:26][CH2:27][CH2:28][C@H:23]1[NH:22][C:2]1[N:7]=[N:6][C:5]([C:8](=[O:9])[NH2:10])=[C:4]([NH:11][C:12]2[N:17]=[C:16]3[N:18]([CH3:21])[CH:19]=[CH:20][C:15]3=[CH:14][CH:13]=2)[CH:3]=1)([CH3:35])([CH3:33])[CH3:34]

Participants

4

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2×HCID 86689730HCID 86689730, compound

Product 1

HCID 86689731{(1S,2R)-2-[6-carbamoyl-5-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl esterYield 18%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

6-Chloro-4-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazine-3-carboxylic acid amide (42 mg, 0.139 mmol), and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (89 mg, 0.416 mmol) were dissolved in N-methylpyrrolidinone (1.4 mL) and heated at 150° C. for 36 h. Additional tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (35 mg, 0.16 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-(1-methyl-1H-pyrrolo[2,3-b]pyridin-6-ylamino)-pyridazin-3-ylamino]-cyclohexyl}-carbamic acid tert-butyl ester (12 mg, 18%) as a light brown amorphous residue. LCMS (EI/CI) m/z: 481 [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-76448f7d08ca46adbe9ee60d46d18c40
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

Loading…