Dimethylacetamide → HCID 118005522, compound

HRID 1478530Notes

Reaction equation

HRID 1478530 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[N:26]=[C:25](Cl)[C:24]([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[C:23]3Cl)([C:10]2[CH:11]=[N:12][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:15]=2)[OH:9])[CH:5]=[CH:6][CH:7]=1.[CH3:38][N:39](C)C(=O)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].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].[C-]#N.[Zn+2].[C-]#N.[Zn]>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]([OH:9])([C:10]2[CH:11]=[N:12][C:13]([C:16]([F:18])([F:19])[F:17])=[CH:14][CH:15]=2)[C:20]2[CH:29]=[C:28]3[C:27](=[CH:22][CH:21]=2)[N:26]=[C:25]([C:38]#[N:39])[C:24]([C:31]2[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=2)=[CH:23]3)[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 2

HCID 31374DimethylacetamideHCID 90101573HCID 90101573, compound2×

Product 1

HCID 118005522HCID 118005522, compound

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
120 °C

Procedure

A pressure tube containing (3-chlorophenyl)(2,4-dichloro-3-phenylquinolin-6-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol (94 mg, 0.17 mmol, Intermediate 22: step b), Pd2(dba)3 (8.0 mg, 0.0087 mmol), 1,1′-bis(diphenylphosphino)ferrocene (dppf, 10 mg, 0.018 mmol), zinc cyanide (25 mg, 0.21 mmol), and zinc nanopowder (3.0 mg, 0.046 mmol) in N,N-dimethylacetamide (1 mL) was sparged with nitrogen for 5 minutes, and then heated at 120° C. for 1 hour followed by 100° C. for 3 hours. The mixture was allowed to cool to room temperature and filtered through a syringe filter. The filtrate was concentrated in vacuo, then EtOAc and NH4OH (aqueous) were added. The organic layer was separated, and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel column, 30-50% EtOAc in heptane), and then by reverse phase HPLC (water/acetonitrile/0.1% TFA) to provide the title compound as a by-product. 1H NMR (400 MHz, CDCl3) δ 8.76 (d, J=2.02 Hz, 1H), 8.25 (s, 1H), 8.20 (d, J=9.60 Hz, 1H), 7.93 (dd, J=2.02, 8.08 Hz, 1H), 7.75-7.79 (m, 2H), 7.71 (d, J=8.08 Hz 1H), 7.60-7.65 (m, 2H), 7.51-7.58 (m, 3H), 7.32-7.40 (m, 3H), 7.15 (dt, J=1.52, 7.58 Hz, 1H).

Workup

  1. customwas sparged with nitrogen for 5 minutes
  2. temperatureto cool to room temperature
  3. filtrationfiltered through a syringe
  4. filtrationfilter
  5. concentrationThe filtrate was concentrated in vacuo
  6. additionEtOAc and NH4OH (aqueous) were added
  7. customThe organic layer was separated
  8. extractionthe aqueous layer was extracted with EtOAc
  9. dry with materialThe combined organic layers were dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe residue was purified by flash column chromatography (silica gel column, 30-50% EtOAc in heptane)

Sources & evidence

ORD record
ord-94c8bdca550643d397900eb5e10e15ba
Source dataset
uspto-grants-2016_08
Patent number
US09403816B2

Reaction notes

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