(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689795, compound

HRID 1396459Notes

Reaction equation

HRID 1396459 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]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[N:13]=2)[CH:3]=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:8]([C:5]1[N:6]=[N:7][C:2]([NH:23][C@@H:24]2[CH2:29][CH2:28][CH2:27][CH2:26][C@@H:25]2[NH:30][C:31](=[O:37])[O:32][C:33]([CH3:35])([CH3:34])[CH3:36])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([C:21]#[N:22])([CH3:20])[CH3:19])[N:13]=1)(=[O:9])[NH2:10]

Participants

4

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected2×HCID 86689794HCID 86689794, compound

Product 1

HCID 86689795HCID 86689795, compoundYield 35.2%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

A resealable pressure tube was charged with 6-chloro-4-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazine-3-carboxamide (200 mg, 631 μmol) and tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (135 mg, 631 μmol) in NMP (2.00 mL). The reaction mixture was heated in an oil bath with stirring at 120° C. for 18 h. Then added more tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (135 mg, 631 μmol) in small portions during 7 hours and reaction continued for 18 h. The solvent was distilled off under high vacuum. The residue was dissolved in dichloromethane containing few drops of methanol and then purified by flash column (spherical silica 20-45 μM, 50 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to yield tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-(2-cyanopropan-2-yl)pyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (110 mg, 222 μmol, 35.2% yield) as a yellow foam. 1H NMR (CHLOROFORM-d) δ: 11.48 (s, 1H), 8.82 (br. s., 1H), 8.00-8.11 (m, 1H), 7.62 (t, J=7.9 Hz, 1H), 6.89 (d, J=7.6 Hz, 1H), 6.79 (d, J=8.3 Hz, 1H), 5.53-5.85 (m, 2H), 5.06 (d, J=8.3 Hz, 1H), 4.47 (br. s., 1H), 3.80-3.99 (m, 1H), 1.24-1.93 (m, 23H); LC-MS 495.1 [M+H]+.

Workup

  1. temperatureThe reaction mixture was heated in an oil bath
  2. customreaction
  3. waitcontinued for 18 h
  4. distillationThe solvent was distilled off under high vacuum
  5. dissolutionThe residue was dissolved in dichloromethane containing few drops of methanol
  6. custompurified by flash column (spherical silica 20-45 μM, 50 g, Versaflash Supelco)
  7. washeluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2

Sources & evidence

ORD record
ord-b8619cba9e1346ff8eccee29b7b035ba
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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