Pyridine → HCID 57845324, compound

HRID 734855Notes

Reaction equation

HRID 734855 reaction equation
S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]#[C:19][C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]=[C:25]([CH2:30]O)[CH:24]=[C:23]4[CH3:32])=[N:16][CH:17]=2)=[CH:8][CH:7]=1.N1C=CC=CC=1.[CH3:39][CH:40]1[CH2:45][CH2:44][NH:43][CH2:42][CH2:41]1>C(Cl)Cl>[Cl:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:13]=[CH:14][C:15]([C:18]#[C:19][C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[N:26]=[C:25]([CH2:30][N:43]3[CH2:44][CH2:45][CH:40]([CH3:39])[CH2:41][CH2:42]3)[CH:24]=[C:23]4[CH3:32])=[N:16][CH:17]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 24386Thionyl ChlorideHCID 693814-MethylpiperidineHCID 69054010HCID 69054010, compound

Product 1

HCID 57845324HCID 57845324, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

16 μL (0.20 mmol) of thionyl chloride was added at RT to a solution of 50 mg (0.13 mmol) of {6-[5-(4-chlorophenyl)pyridin-2-ylethynyl]-4-methylquinolin-2-yl}methanol and 52 μL (0.65 mmol) of pyridine in 3 mL of DCM and the mixture was stirred for 2 hours at RT. The reaction mixture was diluted with DCM, and the organic phase was washed with saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and evaporated down in vacuo. The residue was taken up in 3 mL of DMF, combined with 60 μL (0.51 mmol) of 4-methylpiperidine and stirred for 16 hours at RT. The reaction mixture was evaporated down in vacuo, diluted with DCM, and the organic phase was washed with saturated aqueous sodium bicarbonate solution, dried over magnesium sulfate and evaporated down in vacuo. The crude product was purified by column chromatography (silica gel, gradient DCM/MeOH/sat. aqueous ammonia 100:0:0 95:5:0.5) and HPLC-MS (Zorbax Bonus C18 amide-phase 5 μm, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v). Yield: 4 mg (7% of theoretical); C30H28ClN3 (M=466.016); calc.: molpeak (M+H)+: 466/468 (Cl); found: molpeak (M+H)+: 466/468 (Cl); Rf value: 0.38 (silica gel, DCM/MeOH/sat. aqueous ammonia 9:1:0.1).

Workup

  1. washthe organic phase was washed with saturated aqueous sodium bicarbonate solution
  2. dry with materialdried over magnesium sulfate
  3. customevaporated down in vacuo
  4. stirringstirred for 16 hours at RT
  5. customThe reaction mixture was evaporated down in vacuo
  6. additiondiluted with DCM
  7. washthe organic phase was washed with saturated aqueous sodium bicarbonate solution
  8. dry with materialdried over magnesium sulfate
  9. customevaporated down in vacuo
  10. customThe crude product was purified by column chromatography (silica gel, gradient DCM/MeOH/sat. aqueous ammonia 100:0:0 95:5:0.5) and HPLC-MS (Zorbax Bonus C18 amide-phase 5 μm, gradient 0.15% formic acid in water/acetonitrile 10/90→90/10 v/v)

Sources & evidence

ORD record
ord-38e389e92db64ab189d76deaedb3a4fc
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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