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

HRID 624874Notes

Reaction equation

HRID 624874 reaction equation
[CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([NH:14][C:15]3([C:18]([F:21])([F:20])[F:19])[CH2:17][CH2:16]3)=[O:13])[CH:9]=[CH:8][C:7]=2[N:22]2[CH2:25][C:24]([F:27])([F:26])[CH2:23]2)[CH2:3][CH2:2]1.[CH3:28][C:29]([O-])(CC)C.[Na+].ICC>CN(C=O)C>[CH2:28]([N:14]([C:15]1([C:18]([F:21])([F:20])[F:19])[CH2:16][CH2:17]1)[C:12]([C:10]1[CH:9]=[CH:8][C:7]([N:22]2[CH2:25][C:24]([F:27])([F:26])[CH2:23]2)=[C:6]([O:5][CH2:4][CH:1]2[CH2:3][CH2:2]2)[N:11]=1)=[O:13])[CH3:29]

Participants

5

Reactant 3

HCID 6340IodoethaneHCID 2733478Sodium 2-methylbutan-2-olateHCID 71105762HCID 71105762, compound

Product 1

HCID 762835796-Cyclopropylmethoxy-5-(3,3-difluoro-azetidin-1-yl)-pyridine-2-carboxylic acid ethyl-(1-trifluoromethyl-cyclopropyl)-amideYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 6-(cyclopropylmethoxy)-5-(3,3-difluoroazetidin-1-yl)-N-(1-(trifluoromethyl)cyclopropyl)picolinamide (Example 16 a), 15 mg, 38 μmol) and sodium 2-methylbutan-2-olate (5 mg, 46 μmol) in DMF (150 μL) was stirred for 15 minutes at ambient temperature. Iodoethane (9 mg, 7 μL, 58 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/brine (2×20 mL), dried over Na2SO4 and brought to dryness. The crude product was purified by preparative TLC (silica gel, 1 mm, heptan/EtOAc 2:1, elution with EtOAc) to give the title compound (12 mg, 75%) as colorless oil; MS (EI): m/e=420.2 [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/brine (2×20 mL)
  4. dry with materialdried over Na2SO4
  5. customThe crude product was purified by preparative TLC (silica gel, 1 mm, heptan/EtOAc 2:1, elution with EtOAc)

Sources & evidence

ORD record
ord-b290775e0bcf405ca092885137aeebfd
Source dataset
uspto-grants-2016_04
Patent number
US09303012B2

Reaction notes

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