Methyl iodide → HCID 136352239, compound

HRID 1853300Notes

Reaction equation

HRID 1853300 reaction equation
C([O:5][N:6]=[C:7]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[O:10][C:9]([C:17]2[CH:18]=[C:19]3[CH:25]=[CH:24][NH:23][C:20]3=[CH:21][N:22]=2)=[CH:8]1)(C)(C)C.[C:26]([O:30]N=C1C2C(=CC=CC=2)OC(C2C=C3C=CN(O)C3=CN=2)=C1)(C)(C)C.[H-].[Na+].IC>CN(C)C=O.[Cl-].[Na+].O.ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[CH3:26][O:30][N:23]1[C:20]2=[CH:21][N:22]=[C:17]([C:9]3[O:10][C:11]4[C:16]([C:7](=[N:6][OH:5])[CH:8]=3)=[CH:15][CH:14]=[CH:13][CH:12]=4)[CH:18]=[C:19]2[CH:25]=[CH:24]1

Participants

9

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 86673068HCID 86673068, compoundHCID 86673069HCID 86673069, compound

Product 1

HCID 136352239HCID 136352239, compound

Reagents, catalysts & solvents 4

HCID 24193Titanium TetrachlorideCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
0 °C

Procedure

A 70/30 mixture of 2-(1H-Pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one O-tert-butyl-oxime and 2-(1-Hydroxy-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one O-tert-butyl-oxime (77 mg) in dimethylformamide (5 ml) was cooled to 0° C. and treated with sodium hydride (60% in mineral oil, 10 mg, 0.25 mmol) and stirred at room temperature for 1 hour. The solution was cooled down to 0° C. and treated with iodomethane (16 μl, 0.25 mmol). The solution was slowly warmed up to room temperature during 1 hour and poured into brine, extracted with ethyl acetate, washed with brine, dried over sodium sulfate and concentrated to dryness. The crude mixture of 2-(1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one O-tert-butyl-oxime and 2-(1-methoxy-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one O-tert-butyl-oxime was treated with titanium tetrachloride (0.70 mmol) in dichloromethane (7.5 ml) (method D) to yield separately after purification by preparative HPLC (gradient 65-50% Water/Methanol+0.05% trifluoroacetic acid), 2-(1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one oxime (example 77, 17 mg) and 2-(1-methoxy-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one oxime (example 78, 12 mg) as yellow solids.

Workup

  1. temperatureThe solution was cooled down to 0° C.
  2. temperatureThe solution was slowly warmed up to room temperature during 1 hour
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated to dryness
  7. additionThe crude mixture of 2-(1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one O-tert-butyl-oxime and 2-(1-methoxy-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one O-tert-butyl-oxime
  8. customto yield separately
  9. customafter purification by preparative HPLC (gradient 65-50% Water/Methanol+0.05% trifluoroacetic acid), 2-(1-methyl-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one oxime (example 77, 17 mg) and 2-(1-methoxy-1H-pyrrolo[2,3-c]pyridin-5-yl)-chromen-4-one oxime (example 78, 12 mg) as yellow solids

Sources & evidence

ORD record
ord-8e2bc20314c441639b264ac2b4a63dd0
Source dataset
uspto-grants-2015_02
Patent number
US08962627B2

Reaction notes

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