Sodium Carbonate → 6-benzyl-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80770Notes

Reaction equation

HRID 80770 reaction equation
[CH2:1]([N:8]1[CH2:20][CH2:19][C:11]2[N:12]=[C:13](Cl)[N:14]=[C:15]([O:16][CH3:17])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[CH:28][C:29]=2B2OC(C)(C)C(C)(C)O2)[N:24]([S:40]([C:43]2[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=2)(=[O:42])=[O:41])[CH:23]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOCC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:1]([N:8]1[CH2:20][CH2:19][C:11]2[N:12]=[C:13]([C:29]3[CH:28]=[CH:27][CH:26]=[C:25]4[C:30]=3[C:22]([CH3:21])=[CH:23][N:24]4[S:40]([C:43]3[CH:49]=[CH:48][C:46]([CH3:47])=[CH:45][CH:44]=3)(=[O:42])=[O:41])[N:14]=[C:15]([O:16][CH3:17])[C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 712404273-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indoleHCID 866902516-Benzyl-2-chloro-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 712405256-benzyl-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

To a solution of 6-benzyl-2-chloro-4-methoxy-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.0 g, 3.45 mmol) in DME (10.0 mL) in a 20 mL microwave reaction vial was added 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole (1.57 g, 3.80 mmol). Then 2 M aqueous Na2CO3 (5.6 mL, 11.22 mmol) was added. The reaction mixture was degassed via a series of 3 argon/vacuum cycles and then placed under an atmosphere of argon. Then Pd(Ph3P)4 (0.399 g, 0.345 mmol) was added and the vial was sealed and heated via microwave irradiation at 140° C. for 90 minutes. The reaction mixture was cooled to room temperature and diluted with Et2O and water. The layers were separated and the organic layer was washed with brine, dried over MgSO4, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (27-48% ethyl acetate/heptanes) to provide 6-benzyl-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine as a white solid. MS (ESI+) m/z 539.3 (M+H)+.

Workup

  1. customThe reaction mixture was degassed via a series of 3 argon/vacuum cycles
  2. customthe vial was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe layers were separated
  5. washthe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by silica gel flash chromatography (27-48% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-07914b4e5b164036908ed3ca7bd28543
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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