Ethanol → 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80807Notes

Reaction equation

HRID 80807 reaction equation
C(O)C.[Cl:4][C:5]1[C:6]([CH:49]([CH3:51])[CH3:50])=[N:7][N:8]([CH3:48])[C:9]=1[N:10]1[CH2:47][CH2:46][C:13]2[N:14]=[C:15]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:45])=[CH:29][N:30]4S(C3C=CC(C)=CC=3)(=O)=O)[N:16]=[C:17]([N:18]3[CH2:23][CH2:22][CH2:21][C:20]([CH3:25])([CH3:24])[CH2:19]3)[C:12]=2[CH2:11]1.[OH-].[K+].[OH-].[NH4+]>ClCCl.O>[Cl:4][C:5]1[C:6]([CH:49]([CH3:51])[CH3:50])=[N:7][N:8]([CH3:48])[C:9]=1[N:10]1[CH2:47][CH2:46][C:13]2[N:14]=[C:15]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:45])=[CH:29][NH:30]4)[N:16]=[C:17]([N:18]3[CH2:23][CH2:22][CH2:21][C:20]([CH3:25])([CH3:24])[CH2:19]3)[C:12]=2[CH2:11]1

Participants

7

Reactant 4

HCID 702EthanolHCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 712405676-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 712447426-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Ethanol (1.8 mL) was added to 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (74 mg, 0.108 mmol) in a microwave vial. Next, KOH (61 mg, 1.08 mmol) was added followed by 28% aqueous ammonium hydroxide (0.6 mL, 4.35 mmol). The vessel was sealed and heated via microwave irradiation at 100° C. for 75 minutes. The reaction mixture was cooled to room temperature and diluted with dichloromethane and water. The layers were separated and the organic layer was dried by passing through a phase separator. The eluent was concentrated and the resulting residue was purified by reverse phase HPLC (20-55% MeCN/Water (0.1% TFA)). The eluent from the HPLC was neutralized with saturated aqueous sodium bicarbonate and extracted with dichloromethane. The organic extract was dried by passing through a phase separator and concentrating to provide 6-(4-chloro-3-isopropyl-1-methyl-1H-pyrazol-5-yl)-4-(3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine.

Workup

  1. customThe vessel was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe layers were separated
  4. customthe organic layer was dried
  5. concentrationThe eluent was concentrated
  6. customthe resulting residue was purified by reverse phase HPLC (20-55% MeCN/Water (0.1% TFA))
  7. extractionextracted with dichloromethane
  8. extractionThe organic extract
  9. customwas dried
  10. concentrationconcentrating

Sources & evidence

ORD record
ord-dfa0d04715a6440982c5f98e234893cf
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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