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

HRID 80771Notes

Reaction equation

HRID 80771 reaction equation
C([N:8]1[CH2:39][CH2:38][C:11]2[N:12]=[C:13]([C:18]3[CH:26]=[CH:25][CH:24]=[C:23]4[C:19]=3[C:20]([CH3:37])=[CH:21][N:22]4[S:27]([C:30]3[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[N:14]=[C:15]([O:16][CH3:17])[C:10]=2[CH2:9]1)C1C=CC=CC=1.O.C(O)(=O)C>C1COCC1.C(OCC)(=O)C.C([O-])(O)=O.[Na+].[OH-].[OH-].[Pd+2].[C]>[CH3:17][O:16][C:15]1[C:10]2[CH2:9][NH:8][CH2:39][CH2:38][C:11]=2[N:12]=[C:13]([C:18]2[CH:26]=[CH:25][CH:24]=[C:23]3[C:19]=2[C:20]([CH3:37])=[CH:21][N:22]3[S:27]([C:30]2[CH:36]=[CH:35][C:33]([CH3:34])=[CH:32][CH:31]=2)(=[O:29])=[O:28])[N:14]=1

Participants

8

Reactant 3

HCID 176Acetic AcidHCID 962WaterHCID 712405256-benzyl-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 712404804-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 4

HCID 178502593HCID 178502593, compoundCatalystHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 6-benzyl-4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (1.1 g, 2.0 mmol) in THF (15 mL) was added water (3.75 mL) and acetic acid (0.34 mL, 5.9 mmol), then 20 mol % Pd(OH)2/carbon (50% wet) (0.86 g, 0.61 mmol) was added. The reaction mixture was placed under an atmosphere of hydrogen gas via balloon. After 1.5 hours the mixture was diluted with ethyl acetate and neutralized with saturated aqueous NaHCO3. The mixture was then filtered through a pad of Celite®. The eluent was then further diluted with ethyl acetate and brine and the layers were separated. The organic layer was dried over Na2SO4, filtered, and concentrated. The resulting residue was purified by silica gel flash chromatography (0-20% MeOH/DCM) to provide 4-methoxy-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.91 (d, J=1.0 Hz, 3 H) 2.32 (s, 3 H) 2.68 (t, J=5.6 Hz, 2 H) 3.00 (t, J=5.7 Hz, 2 H) 3.72 (s, 2H) 3.92 (s, 3 H) 7.30-7.48 (m, 4 H) 7.65 (d, J=1.0 Hz, 1 H) 7.85 (d, J=8.3 Hz, 2 H) 8.04 (dd, J=7.3, 2.0 Hz, 1 H). MS (ESI+) m/z 449.2 (M+H)+.

Workup

  1. filtrationThe mixture was then filtered through a pad of Celite®
  2. additionThe eluent was then further diluted with ethyl acetate and brine
  3. customthe layers were separated
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting residue was purified by silica gel flash chromatography (0-20% MeOH/DCM)

Sources & evidence

ORD record
ord-26906e031b7941958b3fd020eec999b9
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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