Dichloromethane → Tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate

HRID 1620044Notes

Reaction equation

HRID 1620044 reaction equation
ClC(Cl)(Cl)C(Cl)=O.ClCCl.[NH2:11][C:12]([C:14]1[CH:15]=[C:16]([F:36])[C:17]([NH:21][C@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[N:18][C:19]=1[Cl:20])=O>C(N(CC)CC)C>[Cl:20][C:19]1[N:18]=[C:17]([NH:21][C@H:22]2[CH2:27][CH2:26][CH2:25][CH2:24][C@H:23]2[NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:32])[CH3:33])[C:16]([F:36])=[CH:15][C:14]=1[C:12]#[N:11]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 6420Trichloroacetyl chlorideHCID 86683847Tert-butyl cis-2-(5-aminocarbonyl-6-chloro-3-fluoropyridin-2-ylamino)cyclohexylcarbamate

Product 1

HCID 86683848Tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamateYield 76%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent

Procedure

Trichloroacetyl chloride (0.55 ml) was added dropwise to a dichloromethane (17 ml) suspension containing tert-butyl cis-2-(5-aminocarbonyl-6-chloro-3-fluoropyridin-2-ylamino)cyclohexylcarbamate (1.74 g) and triethylamine (1.38 ml) under ice cooling, followed by stirring at room temperature for 1 hour. The solvent was distilled away under reduced pressure, and a saturated aqueous ammonium chloride solution and ethyl acetate were added. The organic layer was collected, washed with saturated saline, and dried over anhydrous magnesium sulfate, and then the solvent was distilled away under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 3:1), diisopropylether was added, solid matter was collected by filtration, and a white solid of tert-butyl cis-2-(6-chloro-5-cyano-3-fluoropyridin-2-ylamino)cyclohexylcarbamate (1.26 g) was thus obtained.

Workup

  1. distillationThe solvent was distilled away under reduced pressure
  2. additiona saturated aqueous ammonium chloride solution and ethyl acetate were added
  3. customThe organic layer was collected
  4. washwashed with saturated saline
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationthe solvent was distilled away under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=10:0 to 3:1), diisopropylether
  8. additionwas added
  9. filtrationsolid matter was collected by filtration

Sources & evidence

ORD record
ord-bfd60118006945598c10c16609d792b1
Source dataset
uspto-grants-2014_07
Patent number
US08772320B2

Reaction notes

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