Dimethylformamide → HCID 89600926, compound

HRID 514216Notes

Reaction equation

HRID 514216 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([C:9]2[C:10](=[O:23])[CH:11]([CH2:16][C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=3)[CH2:12][C:13]=2[O:14][CH3:15])=[C:4]([Cl:24])[CH:3]=1.[F-].[Cs+].[CH2:27]([Sn](CCCC)(CCCC)C#CC)[CH2:28][CH2:29]C.CN(C)C=O>O.CCOCC.[Cu]I.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe]>[Cl:8][C:6]1[CH:7]=[C:2]([C:27]#[C:28][CH3:29])[CH:3]=[C:4]([Cl:24])[C:5]=1[C:9]1[C:10](=[O:23])[CH:11]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[CH2:12][C:13]=1[O:14][CH3:15]

Participants

9

Reactant 4

HCID 6228DimethylformamideHCID 25953Cesium fluoride2×HCID 2733165Tributyl(prop-1-yn-1-yl)stannane2×HCID 89601788HCID 89601788, compound

Product 1

HCID 89600926HCID 89600926, compoundYield 32.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 53485975CID 53485975Catalyst2×HCID 962WaterSolventHCID 3283Diethyl EtherSolvent

Conditions

Temperature
120 °C

Procedure

A microwave vial was charged with 2-(4-bromo-2,6-dichloro-phenyl)-3-methoxy-5-(2-pyridylmethyl)cyclopent-2-en-1-one (90 mg, 0.21 mmol), caesium fluoride (CsF, 64 mg, 0.42 mmol), copper(I) iodide (CuI, 8 mg, 0.042 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (23 mg, 0.032 mmol), tributyl(prop-1-ynyl)stannane (83 mg, 0.25 mmol) and N,N-dimethylformamide (0.9 ml), sealed and heated at 120°C. under microwave irradiation for 30 minutes. Further caesium fluoride (32 mg, 0.21 mmol), copper(I) iodide (4 mg, 0.021 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (12 mg, 0.016 mmol) and tributyl(prop-1-ynyl)stannane (42 mg, 0.13 mmol) were added and the reaction heated at 120°C. under microwave irradiation for a further 30 minutes. The reaction was allowed to cool to room temperature, diluted with water (10 ml) and Et2O (10 ml) and filtered through Celite. The filtrate phases were separated and the aqueous phase extracted with further Et2O (2×10 ml). The combined organic extracts were washed with brine (10 ml), dried over MgSO4, filtered and evaporated to dryness under reduced pressure. The crude product was dissolved in EtOAc, absorbed onto silica and purified by flash chromatography on silica using an EtOAc/isohexane gradient to give the desired product (26 mg, 32%). 1H NMR (400 MHz, CDCl3)δ ppm 8.50 (d, 1H), 7.60 (dd, 1H), 7.30 (2×s, 2×1H), 7.25 (d, 1H), 7.15 (dd, 1H), 3.75 (s, 3H), 3.40-3.35 (m, 1H), 3.20-3.10 (m, 1H), 3.00-2.90 (m, 1H), 2.85-2.80 (m, 2H), 2.05 (s, 3H).

Workup

  1. customsealed
  2. temperaturethe reaction heated at 120°C. under microwave irradiation for a further 30 minutes
  3. temperatureto cool to room temperature
  4. filtrationfiltered through Celite
  5. customThe filtrate phases were separated
  6. extractionthe aqueous phase extracted with further Et2O (2×10 ml)
  7. washThe combined organic extracts were washed with brine (10 ml)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. customevaporated to dryness under reduced pressure
  11. dissolutionThe crude product was dissolved in EtOAc
  12. customabsorbed onto silica
  13. custompurified by flash chromatography on silica using an EtOAc/isohexane gradient

Sources & evidence

ORD record
ord-bb0b6291328141afa60957332424a6a2
Source dataset
uspto-grants-2015_08
Patent number
US09107415B2

Reaction notes

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