Water → (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

HRID 80773Notes

Reaction equation

HRID 80773 reaction equation
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:50])=[C:8]([N:10]2[CH2:49][CH2:48][C:13]3[N:14]=[C:15]([C:28]4[CH:36]=[CH:35][CH:34]=[C:33]5[C:29]=4[C:30]([CH3:47])=[CH:31][N:32]5S(C4C=CC(C)=CC=4)(=O)=O)[N:16]=[C:17]([N:18]4[CH2:23][CH2:22][C@H:21]([O:24][CH3:25])[C:20]([CH3:27])([CH3:26])[CH2:19]4)[C:12]=3[CH2:11]2)[CH:9]=1)([CH3:3])[CH3:2].[OH-].[K+].[OH-].[NH4+].O>CO.ClCCl.[Cl-].[Na+].O>[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([CH3:50])=[C:8]([N:10]2[CH2:49][CH2:48][C:13]3[N:14]=[C:15]([C:28]4[CH:36]=[CH:35][CH:34]=[C:33]5[C:29]=4[C:30]([CH3:47])=[CH:31][NH:32]5)[N:16]=[C:17]([N:18]4[CH2:23][CH2:22][C@H:21]([O:24][CH3:25])[C:20]([CH3:26])([CH3:27])[CH2:19]4)[C:12]=3[CH2:11]2)[CH:9]=1)([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 962WaterHCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 71240512(S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-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 71240579(S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (135 mg, 0.195 mmol) in methanol (2 mL) in a microwave vial was added KOH (100 mg, 1.75 mmol) followed by 28% ammonium hydroxide in water (1 mL, 7.25 mmol). The vial was sealed and heated via microwave irradiation at 80° C. for 75 minutes. The reaction mixture was cooled to room temperature and diluted with dichloromethane and brine. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane. The organic layers were combined, dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (0-70% ethyl acetate/heptanes) to furnish (S)-6-(5-isopropyl-2-methylphenyl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (s, 3 H) 0.98 (s, 3 H) 1.18 (d, J=6.8 Hz, 6 H) 1.51-1.62 (m, 1 H) 1.91-1.99 (m, 1 H) 2.01 (s, 3 H) 2.21 (s, 3 H) 2.78-2.88 (m, 2 H) 2.91-3.08 (m, 4 H) 3.29 (s, 3 H) 3.31-3.41 (m, 3 H) 3.60-3.71 (m, 1 H) 4.07 (s, 2 H) 6.86 (d, J=7.3 Hz, 1 H) 6.96 (s, 1 H) 7.07-7.15 (m, 3 H) 7.20 (d, J=7.1 Hz, 1H) 7.41 (d, J=7.8 Hz, 1 H) 10.89 (br. s., 1 H); MS (ESI+) m/z 538.4 (M+H)+.

Workup

  1. customThe vial was sealed
  2. temperatureThe reaction mixture was cooled to room temperature
  3. customThe layers were separated
  4. extractionthe aqueous layer was extracted two additional times with dichloromethane
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel flash chromatography (0-70% ethyl acetate/heptanes)

Sources & evidence

ORD record
ord-c39960c2e0f545feb6664605dbf13671
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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