Dimethylformamide → HCID 22136478, compound

HRID 1827272Notes

Reaction equation

HRID 1827272 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1)#[CH:2].Cl[C:10]1[CH:19]=[C:18]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([Cl:26])[CH:21]=2)[C:17]2[C:12](=[CH:13][CH:14]=[C:15]([C:27]([C:35]3[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=3)([C:29]3[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=3)[OH:28])[CH:16]=2)[N:11]=1.CN(C=O)C>C(NCC)C.C(OCC)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[Cl:26][C:22]1[CH:21]=[C:20]([C:18]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:27]([C:35]4[CH:36]=[CH:37][C:38]([Cl:41])=[CH:39][CH:40]=4)([C:29]4[N:33]([CH3:34])[CH:32]=[N:31][CH:30]=4)[OH:28])[CH:16]=3)[N:11]=[C:10]([C:2]#[C:1][C:3]3[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=3)[CH:19]=2)[CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 3

HCID 6228DimethylformamideHCID 10821PhenylacetyleneHCID 22136494HCID 22136494, compound

Product 1

HCID 22136478HCID 22136478, compoundYield 18%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 3283Diethyl EtherSolventHCID 8021DiethylamineSolvent

Procedure

A mixture of ethynyl-benzene (0.0021 mol), Pd(PPh3)2Cl2(0.0002 mol) and copper (I) iodide (0.0002 mol) was added at room temperature to a mixture of (±)-2-chloro-4-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-6-quinolinemethanol (0.0014 mol), described in International Patent Specification WO 00/39082, in N-ethyl-ethanamine (7ml) and DMF (7 ml) under N2 flow. The mixture was stirred at room temperature overnight, then at room temperature for 3 days, poured out into ice water and extracted with EtOAc. The organic layer was separated, washed three times with water, dried (MgSO4), filtered and the solvent was evaporated. The residue (1.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 100 to CH2Cl2/CH3OH 98/2 98/2; 35–70 μm). The pure fractions were collected and the solvent was evaporated, yielding 0.5 g of a fraction which was taken up in diethyl ether. The precipitate was filtered off and dried. The residue (0.28 g) was purified by column chromatography over kromasil (eluent: CH3CN/CH3COONH4 1% 75/25; 10 μm). The pure fractions were collected and the solvent was evaporated, yielding: 0.279 g of a product which was dried at 90° C. in a vacuum for 4 hours, yielding 0.14 g (18%) of 4-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-2-(phenylethynyl)-6-quinolinemethanol, mp. 154° C.

Workup

  1. waitat room temperature for 3 days
  2. extractionextracted with EtOAc
  3. customThe organic layer was separated
  4. washwashed three times with water
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customthe solvent was evaporated
  8. customThe residue (1.2 g) was purified by column chromatography over silica gel (eluent: CH2Cl2 100 to CH2Cl2/CH3OH 98/2 98/2; 35–70 μm)
  9. customThe pure fractions were collected
  10. customthe solvent was evaporated
  11. customyielding 0.5 g of a fraction which
  12. filtrationThe precipitate was filtered off
  13. customdried
  14. customThe residue (0.28 g) was purified by column chromatography over kromasil (eluent: CH3CN/CH3COONH4 1% 75/25; 10 μm)
  15. customThe pure fractions were collected
  16. customthe solvent was evaporated
  17. customyielding
  18. dry with material0.279 g of a product which was dried at 90° C. in a vacuum for 4 hours

Sources & evidence

ORD record
ord-9b21673022354255bcda04a9335d2b8f
Source dataset
uspto-grants-2006_05
Patent number
US07053105B2

Reaction notes

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