Tris(1,1-dimethylethyl)phosphine → HCID 25006742, compound

HRID 2239501Notes

Reaction equation

HRID 2239501 reaction equation
Br[C:2]1[C:7]([F:8])=[CH:6][C:5]([S:9]([NH:12][CH2:13][CH:14]2[CH2:16][CH2:15]2)(=[O:11])=[O:10])=[C:4]([F:17])[CH:3]=1.[C:18]([C:20]1[N:24]([CH3:25])[C:23](B(O)O)=[CH:22][CH:21]=1)#[N:19].[F-].[K+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[C:18]([C:20]1[N:24]([CH3:25])[C:23]([C:2]2[C:7]([F:8])=[CH:6][C:5]([S:9]([NH:12][CH2:13][CH:14]3[CH2:16][CH2:15]3)(=[O:11])=[O:10])=[C:4]([F:17])[CH:3]=2)=[CH:22][CH:21]=1)#[N:19]

Participants

6

Reactant 4

HCID 83681Tris(1,1-dimethylethyl)phosphineHCID 522689Potassium FluorideHCID 11708078(5-cyano-1-methyl-1H-pyrrol-2-yl)boronic acidHCID 68482433Benzenesulfonamide, 4-bromo-N-(cyclopropylmethyl)-2,5-difluoro-

Product 1

HCID 25006742HCID 25006742, compoundYield 26.8%

Reagents, catalysts & solvents 1

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

According to general procedure B, 4-bromo-N-(cyclopropylmethyl)-2,5-difluorobenzenesulfonamide (150 mg, 0.5 mmol), 5-cyano-1-methyl-1H-pyrrol-2-ylboronic acid (90 mg, 0.60 mmol), potassium fluoride (96 mg, 1.65 mmol), and tris(dibenzylideneacetone)dipalladium (12 mg, 0.013 mmol) were placed in an oven dried flask under nitrogen and dry THF (1.3 mL) was added. Tri-t-butylphosphine (75 μL, 0.026 mmol, 10 wt % in hexane) was added and the reaction was stirred for 16 hours. Purification afforded 4-(5-cyano-1-methyl-1H-pyrrol-2-yl)-N-(cyclopropylmethyl)-2,5-difluorobenzenesulfonamide (47 mg). HPLC purity 98.2% at 210-370 nm, 9.5 min.; the Xterra® RP18 column, 3.5μ, 150×4.6 mm column, 1.2 mL/min., 85/15-5/95 (ammonium formate buffer pH=3.5/ACN+MeOH) for 10 min., hold 4 min. HRMS: calcd for C16H15F2N3O2S−H+, 350.07803; found (ESI-FTMS, [M−H]1−), 350.07826

Workup

  1. customwere placed in an oven
  2. customdried flask under nitrogen
  3. additiondry THF (1.3 mL) was added
  4. customPurification

Sources & evidence

ORD record
ord-2048167462d54e08974f0ad71cc99d58
Source dataset
uspto-grants-2010_05
Patent number
US07723332B2

Reaction notes

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