(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protected → HCID 86689756, compound

HRID 1396403Notes

Reaction equation

HRID 1396403 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]([CH:18]3[CH2:21][CH2:20][CH2:19]3)[N: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:8]([C:5]1[N:6]=[N:7][C:2]([NH:22][C@@H:23]2[CH2:28][CH2:27][CH2:26][CH2:25][C@@H:24]2[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[CH:3][C:4]=1[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([CH:18]2[CH2:21][CH2:20][CH2:19]2)[N:13]=1)(=[O:9])[NH2:10]

Participants

4

Reactant 2

HCID 1514389(1S,2R)-Cyclohexane-1,2-diamine, N1-BOC protectedHCID 86689755HCID 86689755, compound

Product 1

HCID 86689756HCID 86689756, compoundYield 25.1%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

In a 25 mL round bottom flask, a solution of 6-chloro-4-(6-cyclobutylpyridin-2-ylamino)pyridazine-3-carboxamide (281 mg, 925 μmol) in N-methyl-2-pyrrolidinone (3.5 mL) was treated with tert-butyl (1S,2R)-2-aminocyclohexylcarbamate (397 mg, 1.85 mmol) and the mixture heated to 120° C. for 72 h. After cooling to room temperature the solvent was evaporated in high vacuum and residue was purified by flash column (spherical silica 20-45 μM, 80 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2 to give tert-butyl (1S,2R)-2-(6-carbamoyl-5-(6-cyclobutylpyridin-2-ylamino)pyridazin-3-ylamino)cyclohexylcarbamate (112 mg, 25.1% yield) as a light brown foam. 1H NMR (CHLOROFORM-d) δ: 11.49 (br. s., 1H), 8.38 (s, 1H), 8.12 (d, J=3.0 Hz, 1H), 7.42 (t, J=7.9 Hz, 1H), 7.23 (s, 1H), 6.67 (d, J=7.2 Hz, 1H), 6.59 (d, J=7.9 Hz, 1H), 5.89-6.22 (m, 2H), 3.72-4.08 (m, 2H), 3.55 (quin, J=8.6 Hz, 1H), 1.76-2.11 (m, 4H), 1.19-1.74 (m, 19H); LC-MS 482.1 [M+H]+.

Workup

  1. temperatureAfter cooling to room temperature the solvent
  2. customwas evaporated in high vacuum and residue
  3. customwas purified by flash column (spherical silica 20-45 μM, 80 g, Versaflash Supelco)
  4. washeluting with 0 to 5% over 20 min (MeOH containing 10% NH4OH)/CH2Cl2

Sources & evidence

ORD record
ord-18ff3557ed2a41eda0168147ca6d1c6b
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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