Triethylamine → N-[5-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzyl]-methanesulfonamide

HRID 606915Notes

Reaction equation

HRID 606915 reaction equation
C(N(CC)CC)C.Br[C:9]1[CH:10]=[N:11][CH:12]=[C:13]([CH:16]=1)[C:14]#[N:15].[F:17][C:18]1[CH:29]=[CH:28][C:27]([C:30]#[C:31][Si](C)(C)C)=[CH:26][C:19]=1[CH2:20][NH:21][S:22]([CH3:25])(=[O:24])=[O:23].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.[Br-].[Zn+2].[Br-].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:14]([C:13]1[CH:16]=[C:9]([C:31]#[C:30][C:27]2[CH:28]=[CH:29][C:18]([F:17])=[C:19]([CH:26]=2)[CH2:20][NH:21][S:22]([CH3:25])(=[O:24])=[O:23])[CH:10]=[N:11][CH:12]=1)#[N:15]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 7367935-BromonicotinonitrileHCID 2724141Tetrabutylammonium Fluoride2×HCID 67047541N-(2-Fluoro-5-trimethylsilanylethynylbenzyl)-methanesulfonamide

Product 1

HCID 67047961N-[5-(5-Cyanopyridin-3-ylethynyl)-2-fluorobenzyl]-methanesulfonamideYield 50.6%

Reagents, catalysts & solvents 3

HCID 10421208Zinc bromideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
60 °C

Procedure

Dissolve zinc (II) bromide (94 mg, 0.36 mmol) in tetrahydrofuran (0.75 mL) and treat with triethylamine (0.20 mL, 1.4 mmol). After 4 min add 5-bromonicotinonitrile (55 mg, 0.30 mmol), N-(2-fluoro-5-trimethylsilanylethynylbenzyl) -methanesulfonamide, (prepared as described in PREPARATION 34), (100 mg, 0.33 mmol) and tetrakis(triphenylphosphine)palladium (0) (17 mg, 0.015 mmol) to the reddish solution. Heat to 60° C. and add a 1 M solution of tetrabutylammonium fluoride (0.36 mL) in tetrahydrofuran. After 1 h add additional 1 M tetrabutylammonium fluoride (0.3 mL) in tetrahydrofuran and stir an additional 30 min. Cool to room temperature and filter through diatomaceous earth washing with ethyl acetate. Purify by silica gel chromatography, eluting with a gradient from 60:40 to 40:60 (7:30 hexanes:dichloromethane):ethyl acetate, to give the title compound as a white crystalline solid (50 mg, 50%).

Workup

  1. temperatureCool to room temperature
  2. filtrationfilter through diatomaceous earth
  3. washwashing with ethyl acetate
  4. customPurify by silica gel chromatography
  5. washeluting with a gradient from 60:40 to 40:60 (7:30 hexanes:dichloromethane)

Sources & evidence

ORD record
ord-54630c9503d6492ba83d33c0591b1825
Source dataset
uspto-grants-2011_03
Patent number
US07915424B2

Reaction notes

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