Pyridine → 4-(6.7-Dimethyl-2,3-dihydro-indol-1-yl)-pyrido[3,4-d]pyrimidine Hydrochloride

HRID 1937408Notes

Reaction equation

HRID 1937408 reaction equation
[Cl:1][C:2]1[C:3]2[CH:11]=[CH:10][N:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:12][C:13]1[C:21]([CH3:22])=[C:20]2[C:16]([CH2:17][CH2:18][NH:19]2)=[CH:15][CH:14]=1.N1C=CC=CC=1>C(O)(C)C>[ClH:1].[CH3:12][C:13]1[C:21]([CH3:22])=[C:20]2[C:16]([CH2:17][CH2:18][N:19]2[C:2]2[C:3]3[CH:11]=[CH:10][N:9]=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 122716344-Chloropyrido(3,4-d)pyrimidineHCID 167924446,7-Dimethyl-2,3-dihydro-1H-indole

Product 1

HCID 224608074-(6.7-Dimethyl-2,3-dihydro-indol-1-yl)-pyrido[3,4-d]pyrimidine HydrochlorideYield 15.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

To 4-chloro-pyrido[3,4-d]pyrimidine (200 mg, 1.21 mmol) in isopropanol (3 mL) was added 6,7-dimethylindoline (211 mg, 1.44 mmol) and pyridine (190 mg, 2.41 mmol). The reaction mixture was heated to reflux under an atmosphere of dry nitrogen for 6 hours. Solvent was removed in vacuo and the residue was dissolved in CHCl3 and washed with saturated aqueous sodium carbonate. The organic phase was dried over sodium sulfate concentrated in vacuo, and flash chromatographed on silica in 45% acetone/hexanes to afford 60 mg of the free base of the title product (LC-MS: 278 (MH+). This material was dissolved in a minimum volume of 10% methanol in methylene chloride and 1 mole equivalent of HCl in ether was added dropwise with stirring. The reaction mixture was diluted with four volumes of ether and the precipitated title product was filtered and dried in vacuo (58 mg; M.P. 248° C.; GC-MS: 277 (M+); anal. RP-HPLC:4.06 min.)

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux under an atmosphere of dry nitrogen for 6 hours
  3. customSolvent was removed in vacuo
  4. dissolutionthe residue was dissolved in CHCl3
  5. washwashed with saturated aqueous sodium carbonate
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. concentrationconcentrated in vacuo, and flash
  8. customchromatographed on silica in 45% acetone/hexanes

Sources & evidence

ORD record
ord-78e00645d25d4fa09a4ec7ef36fd4f24
Source dataset
uspto-grants-2002_05
Patent number
US06395733B1

Reaction notes

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