Ethyl Acetate → Methyl 2-benzylamino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)nicotinate

HRID 1620050

Reaction equation

HRID 1620050 reaction equation
C(N([CH:7]([CH3:9])[CH3:8])CC)(C)C.[C@@H:10]1([NH2:17])[CH2:15][CH2:14][CH2:13][CH2:12][C@@H:11]1[NH2:16].[CH3:18]N1CCCC1=O.[CH2:25]([NH:32][C:33]1[N:42]=[C:41](Cl)[CH:40]=[CH:39][C:34]=1[C:35]([O:37][CH3:38])=[O:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[C:44]([O:47]CC)(=[O:46])C>O>[CH2:25]([NH:32][C:33]1[N:42]=[C:41]([NH:16][C@@H:11]2[CH2:12][CH2:13][CH2:14][CH2:15][C@@H:10]2[NH:17][C:44]([O:47][C:7]([CH3:9])([CH3:18])[CH3:8])=[O:46])[CH:40]=[CH:39][C:34]=1[C:35]([O:37][CH3:38])=[O:36])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1

Participants

7

Reactant 5

HCID 8857Ethyl AcetateHCID 13387N-methyl-2-pyrrolidoneHCID 81531DiisopropylethylamineHCID 3429171,2-Diaminocyclohexane, cis-HCID 86683851Methyl 2-benzylamino-6-chloronicotinate

Product 1

HCID 86683850Methyl 2-benzylamino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)nicotinate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

Diisopropylethylamine (7.5 ml) and cis-cyclohexane-1,2-diamine (5.0 g) were added to an N-methylpyrrolidone (50 ml) solution containing methyl 2-benzylamino-6-chloronicotinate (6.0 g), followed by stirring at 120° C. for 11 hours. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. The organic layer was collected, washed with saturated saline, and dried over anhydrous sodium sulfate, and then the solvent was distilled away under reduced pressure. Di-tert-butyl dicarbonate (4.7 g) was added to a tetrahydrofuran (50 ml) solution containing the obtained residue and the resulting mixture was left at rest at room temperature for 3 days. The solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (silica gel:silica gel 60 (spherical shape) (Kanto Chemical Co., Inc.); hexane:ethyl acetate=3:1), and a light yellow solid of methyl 2-benzylamino-6-(cis-2-(tert-butoxycarbonylamino)cyclohexylamino)nicotinate (7.7 g) was thus obtained.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe organic layer was collected
  3. washwashed with saturated saline
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationthe solvent was distilled away under reduced pressure
  6. additionDi-tert-butyl dicarbonate (4.7 g) was added to a tetrahydrofuran (50 ml) solution
  7. additioncontaining the obtained residue
  8. waitthe resulting mixture was left at rest at room temperature for 3 days
  9. distillationThe solvent was distilled away under reduced pressure
  10. customThe obtained residue was purified by silica gel column chromatography (silica gel:silica gel 60 (spherical shape) (Kanto Chemical Co., Inc.); hexane:ethyl acetate=3:1)

Sources & evidence

ORD record
ord-a726e39ae28e4376b420cfac144a67ab
Source dataset
uspto-grants-2014_07
Patent number
US08772320B2

Linked notes

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