Pyridine → Phenyl(5-cyano-4-(thiophen-2-ylmethoxy)pyridin-2-yl)carbamate

HRID 1778032Notes

Reaction equation

HRID 1778032 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][CH2:21][C:22]2[S:23][CH:24]=[CH:25][CH:26]=2)[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][CH2:21][C:22]3[S:23][CH:24]=[CH:25][CH:26]=3)[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 1049PyridineHCID 15891Phenyl chloroformateHCID 1180368296-Amino-4-(thiophen-2-ylmethoxy)nicotinonitrile2×

Product 1

HCID 131734798Phenyl(5-cyano-4-(thiophen-2-ylmethoxy)pyridin-2-yl)carbamate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Phenyl chloroformate (3.46 ml, 27.6 mmol) was added drop wise to a mixture of 6-amino-4-(thiophen-2-ylmethoxy)nicotinonitrile (intermediate 284, 2.90 g, 12.54 mmol) and pyridine (4.46 ml, 55.2 mmol) in THF (100 ml) at room temperature. The reaction mixture was stirred for 16 h at room temperature and then partitioned between EtOAc and saturated aqueous NaHCO3 solution, the organic layer washed with saturated brine, dried over MgSO4 and evaporated. The residue was purified by normal phase chromatography: 80 g RediSep® column, eluting with a gradient from heptane to EtOAc. Product containing fractions were combined and evaporated to give the title compound as a beige solid. (UPLC-MS 3) tR 1.14; ESI-MS 352.0 [M+H]+.

Workup

  1. custompartitioned between EtOAc and saturated aqueous NaHCO3 solution
  2. washthe organic layer washed with saturated brine
  3. dry with materialdried over MgSO4
  4. customevaporated
  5. customThe residue was purified by normal phase chromatography
  6. wash80 g RediSep® column, eluting with a gradient from heptane to EtOAc
  7. additionProduct containing fractions
  8. customevaporated

Sources & evidence

ORD record
ord-e2b801949cbb4fe0a5de08cee1f57b77
Source dataset
uspto-grants-2016_02
Patent number
US09266883B2

Reaction notes

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