Dimethylformamide → HCID 44224890, compound

HRID 1914543Notes

Reaction equation

HRID 1914543 reaction equation
[N:1]1([C:8]([C:10]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[S:12][C:11]=2Br)=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:22][N:23](C=O)C>[C-]#N.[Zn+2].[C-]#N.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:1]1([C:8]([C:10]2[CH:14]=[C:13]([C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)[S:12][C:11]=2[C:22]#[N:23])=[O:9])[CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 44225123HCID 44225123, compound

Product 1

HCID 44224890HCID 44224890, compound

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalyst

Conditions

Temperature
100 °C

Procedure

Azepan-1-yl-(2-bromo-5-phenyl-thiophen-3-yl)-methanone (109 mg, 0.30 mmol) was dissolved in DMF (2 mL). Zinc cyanide (0.30 mmol) and tetrakis(triphenylphosphine) palladium (0) (0.15 mmol) were added and the reaction heated at 100° C. for 5 hours. The reaction mixture was cooled to ambient temperature, quenched with a 1:1 mixture of 5% aqueous sodium thiosulfate and 10% aqueous potassium carbonate. The resulting mixture was extracted with ethyl acetate, and the organic solvent separated and then evaporated. The residue was purified by HPLC, eluting with 50%-90% acetonitrile in water (0.1% formic acid) over 30 minutes. The fractions containing the desired product were concentrated under vacuum and freeze-dried to give the title compound (16 mg). LCMS m/z 311.10 [M+H]+ R.T.=11.43 min (Analytical Method 2). 1H NMR (400 MHz, CHCl3-d): δ 7.60 (m, 2H), 7.5 (m, 3H), 7.2 (s, 1H), 3.75 (t, 2H), 3.5 (t, 2H), 1.9 (m, 2H), 1.75-1.6 (m, 6H).

Workup

  1. temperatureThe reaction mixture was cooled to ambient temperature
  2. customquenched with a 1:1 mixture of 5% aqueous sodium thiosulfate and 10% aqueous potassium carbonate
  3. extractionThe resulting mixture was extracted with ethyl acetate
  4. customthe organic solvent separated
  5. customevaporated
  6. customThe residue was purified by HPLC
  7. washeluting with 50%-90% acetonitrile in water (0.1% formic acid) over 30 minutes
  8. additionThe fractions containing the desired product
  9. concentrationwere concentrated under vacuum
  10. customfreeze-dried

Sources & evidence

ORD record
ord-365d0de982cf4723b48521d424e65186
Source dataset
uspto-grants-2013_12
Patent number
US08614209B2

Reaction notes

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