Pyridine → (R)-phenyl (5-cyano-4-((1-methoxypropan-2-yl)oxy)pyridin-2-yl)carbamate

HRID 1777978Notes

Reaction equation

HRID 1777978 reaction equation
Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:3].[NH2:11][C:12]1[CH:19]=[C:18]([O:20][C@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[C:15]([C:16]#[N:17])=[CH:14][N:13]=1.N1C=CC=CC=1>C1COCC1>[C:5]1([O:4][C:2](=[O:3])[NH:11][C:12]2[CH:19]=[C:18]([O:20][C@H:21]([CH3:25])[CH2:22][O:23][CH3:24])[C:15]([C:16]#[N:17])=[CH:14][N:13]=2)[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1

Participants

5

Reactant 3

HCID 1049Pyridine2×HCID 15891Phenyl chloroformate2×HCID 118036909(R)-6-amino-4-((1-methoxypropan-2-yl)oxy)nicotinonitrile2×

Product 1

HCID 131734794(R)-phenyl (5-cyano-4-((1-methoxypropan-2-yl)oxy)pyridin-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Phenyl chloroformate (1.53 ml, 12.2 mmol) was added drop wise to a mixture of (R)-6-amino-4-((1-methoxypropan-2-yl)oxy)nicotinonitrile (intermediate 146, 1.37 g, 5.55 mmol) and pyridine (0.99 ml, 12.2 mmol) in THF (60 ml) at 0° C. The reaction mixture was stirred for 12 h at room temperature and additional pyridine (0.98 ml, 12.2 mmol) and phenyl chloroformate (1.53 ml, 12.2 mmol) were added. After stirring for a further 36 h at room temperature the reaction mixture was partitioned between EtOAc and saturated aqueous NaHCO3 solution, the organic layer washed with saturated brine, dried over MgSO4 and evaporated. The residue was triturated with Et2O and the product obtained by filtration as a white solid. (UPLC-MS 6) tR 1.04; ESI-MS 328.4 [M+H]+.

Workup

  1. stirringAfter stirring for a further 36 h at room temperature the reaction mixture
  2. customwas partitioned between EtOAc and saturated aqueous NaHCO3 solution
  3. washthe organic layer washed with saturated brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe residue was triturated with Et2O
  7. customthe product obtained by filtration as a white solid

Sources & evidence

ORD record
ord-7e9fa0da6e514eaf88b30ee82c859e33
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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