Dimethylformamide → HCID 89601525, compound

HRID 514208Notes

Reaction equation

HRID 514208 reaction equation
Br[C:2]1[CH:7]=[C:6]([CH3:8])[C:5]([C:9]2[C:10](=[O:27])[CH:11]([CH2:16][C:17]3[N:22]=[C:21]([NH:23][CH3:24])[C:20]([C:25]#[N:26])=[CH:19][CH:18]=3)[CH2:12][C:13]=2[O:14][CH3:15])=[C:4]([CH3:28])[CH:3]=1.[F-].[Cs+].[CH2:31]([Sn](CCCC)(CCCC)C#CC)[CH2:32][CH2:33]C.CN(C)C=O>O.C(OCC)C.[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]>[CH3:8][C:6]1[CH:7]=[C:2]([C:31]#[C:32][CH3:33])[CH:3]=[C:4]([CH3:28])[C:5]=1[C:9]1[C:10](=[O:27])[CH:11]([CH2:16][C:17]2[N:22]=[C:21]([NH:23][CH3:24])[C:20]([C:25]#[N:26])=[CH:19][CH: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 89600830HCID 89600830, compound

Product 1

HCID 89601525HCID 89601525, compoundYield 24%

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 6-[[3-(4-bromo-2,6-dimethyl-phenyl)-4-methoxy-2-oxo-cyclopent-3-en-1-yl]methyl]-2-(methylamino)pyridine-3-carbonitrile (150 mg, 0.34 mmol), caesium fluoride (CsF, 104 mg, 0.68 mmol), copper(I) iodide (CuI, 13 mg, 0.068 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (37 mg, 0.05 mmol), tributyl(prop-1-ynyl)stannane (125 mg, 0.41 mmol) and N,N-dimethylformamide (1.5 ml), sealed and heated at 120°C. under microwave irradiation for 60 minutes. Further caesium fluoride (52 mg, 0.34 mmol), copper(I) iodide (6.5 mg, 0.034 mmol), dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (18.5 mg, 0.025 mmol) and tributyl(prop-1-ynyl)stannane (63 mg, 0.21 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 diethyl ether (10 ml) and filtered through Celite. The filtrate phases were separated and the aqueous phase extracted with further diethyl ether (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 (32 mg, 24%) as a yellow gum. 1H NMR (400 MHz, CDCl3) 7.45 (d, 1H), 7.05 (2×s, 2×1H), 6.45 (d, 1H), 5.20 (br, 1H), 3.50 (s, 3H), 3.50-3.40 (m, 1H), 3.20-3.15 (m, 1H), 3.05 (d, 3H), 2.80-2.05 (m, 3H), 2.15 (s, 3H), 2.05 (s, 3H), 1.95 (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 diethyl ether (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-3052179721874c6a848e2584e11edf0d
Source dataset
uspto-grants-2015_08
Patent number
US09107415B2

Reaction notes

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