Dimethylformamide → HCID 10449607, compound

HRID 1394920Notes

Reaction equation

HRID 1394920 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:24])=[C:6]([C:8]2[CH2:12][N:11]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])[CH:10]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[CH:9]=2)[CH:7]=1.[CH3:25][N:26](C=O)C>[C-]#N.[Zn+2].[C-]#N.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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[F:24][C:5]1[CH:4]=[CH:3][C:2]([N+:26]#[C-:25])=[CH:7][C:6]=1[C:8]1[CH2:12][N:11]([C:13]([N:15]([CH3:17])[CH3:16])=[O:14])[CH:10]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:9]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 10318130HCID 10318130, compound

Product 1

HCID 10449607HCID 10449607, compound

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Procedure

A deoxygenated solution of 4-(5-bromo-2-fluorophenyl)-N,N-dimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (2-11, 50 mg, 0.13 mmol, 1 equiv), zinc cyanide (10 mg, 0.85 mmol, 0.66 equiv), tris(dibenzylideneacetone)-dipalladium (12 mg, 0.013 mmol, 0.10 equiv), and 1,1′-bis(diphenylphosphino)-ferrocene (17 mg, 0.031 mmol, 0.24 equiv) in DMF (3 mL) was heated at 110° C. for 3 hours. The reaction mixture was partitioned between brine (50 mL) and ethyl acetate (50 mL). The organic layer was dried over sodium sulfate and concentrated. The residue was purified by flash column chromatography (CH2Cl2 initially, grading to 10% EtOAc in CH2Cl2) to provide 4-(2-fluoro-5-isocyanophenyl)-N,N-dimethyl-2-phenyl-2,5-dihydro-1H-pyrrole-1-carboxamide (13-1) as a pale yellow solid. 1H NMR (500 MHz, CDCl3) δ 7.62 (dd, 1H, j=6.8, 2.0 Hz), 7.59 (m, 1H), 7.33 (m, 4H), 7.26 (m, 1H), 7.22 (dd, 1H, J=10.7, 8.8 Hz), 6.49 (br s, 1H), 6.16 (m, 1H), 4.89 (ddd, 1H, J=13.7, 5.6, 2.0 Hz), 4.55 (d, 1H, J=13.7 Hz), 2.89 (s, 6H). LRMS m/z (M+H) 336.05 found, 336.14 required.

Workup

  1. customThe reaction mixture was partitioned between brine (50 mL) and ethyl acetate (50 mL)
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe residue was purified by flash column chromatography (CH2Cl2 initially

Sources & evidence

ORD record
ord-33b71bf71177419884e2cd396ceb416a
Source dataset
uspto-grants-2008_03
Patent number
US07348440B2

Reaction notes

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