Phosphorus oxychloride → 7-(3,4-dihydro-1H-isoquinolin-2-yl)-1-(3-fluorobenzyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-carbaldehyde hydrochloride

HRID 1932362Notes

Reaction equation

HRID 1932362 reaction equation
P(Cl)(Cl)([Cl:3])=O.Cl.[F:7][C:8]1[CH:9]=[C:10]([CH:32]=[CH:33][CH:34]=1)[CH2:11][N:12]1[C:16]2=[C:17]([N:21]3[CH2:30][CH2:29][C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[CH2:22]3)[N:18]=[CH:19][CH:20]=[C:15]2[CH:14]=[C:13]1[CH3:31].[C:35](=O)(O)[O-:36].[Na+]>CN(C)C=O>[ClH:3].[CH2:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH2:29][CH2:30][N:21]1[C:17]1[N:18]=[CH:19][CH:20]=[C:15]2[C:14]([CH:35]=[O:36])=[C:13]([CH3:31])[N:12]([CH2:11][C:10]3[CH:32]=[CH:33][CH:34]=[C:8]([F:7])[CH:9]=3)[C:16]=12

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 67141928HCID 67141928, compound

Product 1

HCID 866152557-(3,4-dihydro-1H-isoquinolin-2-yl)-1-(3-fluorobenzyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-3-carbaldehyde hydrochloride

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

Phosphorus oxychloride (44 μl, 0.47 mmol) was added to a solution of 2-[1-(3-fluorobenzyl)-2-methyl-1H-pyrrolo[2,3-c]pyridin-7-yl]-1,2,3,4-tetrahydroisoquinoline hydrochloride (115 mg, 0.31 mmol) prepared in Example 613 in N,N-dimethylformamide (2 ml). The reaction mixture was stirred overnight at 100° C. under heating. The reaction mixture was cooled to room temperature, added to ice water, basified with a sodium bicarbonate solution, and then extracted with ethyl acetate. The organic layer was dried on anhydrous magnesium sulfate and then concentrated under reduced pressure. The resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/1, v/v). The resulting product was dissolved in ethyl acetate, saturated with hydrochloric acid gas, and then filtered to give 28 mg of the titled compound as a white solid.

Workup

  1. temperatureunder heating
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with ethyl acetate
  4. dry with materialThe organic layer was dried on anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified with silica gel column chromatography (ethyl acetate/n-hexane=1/1, v/v)
  7. dissolutionThe resulting product was dissolved in ethyl acetate, saturated with hydrochloric acid gas
  8. filtrationfiltered

Sources & evidence

ORD record
ord-67da35e630ba47e59d14e5a0b656c33a
Source dataset
uspto-grants-2012_05
Patent number
US08188114B2

Reaction notes

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