Methyl iodide → 6-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid methyl-(1-trifluoromethyl-cyclopropyl)-amide

HRID 624869Notes

Reaction equation

HRID 624869 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]1([NH:6][C:7]([C:9]2[CH:14]=[CH:13][C:12]([N:15]3[CH2:18][C:17]([F:20])([F:19])[CH2:16]3)=[C:11]([O:21][CH2:22][CH:23]3[CH2:25][CH2:24]3)[N:10]=2)=[O:8])[CH2:5][CH2:4]1.[H-].[Na+].I[CH3:31]>CN(C=O)C>[CH3:31][N:6]([C:3]1([C:2]([F:1])([F:26])[F:27])[CH2:4][CH2:5]1)[C:7]([C:9]1[CH:14]=[CH:13][C:12]([N:15]2[CH2:18][C:17]([F:20])([F:19])[CH2:16]2)=[C:11]([O:21][CH2:22][CH:23]2[CH2:24][CH2:25]2)[N:10]=1)=[O:8]

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 71105762HCID 71105762, compound

Product 1

HCID 762818776-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid methyl-(1-trifluoromethyl-cyclopropyl)-amideYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid (1-trifluoromethyl-cyclopropyl)-amide (20 mg, 51.1 μmol) and sodium hydride (3.3 mg, 76.7 μmol) in DMF (0.2 mL) was stirred for 15 min. at ambient temperature. Iodomethane (14.5 mg, 6.38 μL, 102 μmol) was added and stirring was continued for 1 h. The reaction mixture was poured onto ice/sat. aqueous NaHCO3 solution (15 mL) and extracted with EtOAc (2×25 mL). The combined extracts were washed with ice water/brine (2×20 mL), dried over Na2SO4 and brought to dryness. The crude brown oil was purified by preparative TLC (silica gel, 1 mm, heptan/EtOAc 4:1, elution with EtOAc) to give the title compound (13 mg, 63%) as colorless oil; MS (EI): m/e=406.4 [MH]+.

Workup

  1. additionThe reaction mixture was poured onto ice/
  2. extractionaqueous NaHCO3 solution (15 mL) and extracted with EtOAc (2×25 mL)
  3. washThe combined extracts were washed with ice water/brine (2×20 mL)
  4. dry with materialdried over Na2SO4
  5. customThe crude brown oil was purified by preparative TLC (silica gel, 1 mm, heptan/EtOAc 4:1, elution with EtOAc)

Sources & evidence

ORD record
ord-7c83e67cf8194307ac38298a1fbd8c10
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

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