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

HRID 80782Notes

Reaction equation

HRID 80782 reaction equation
C([N:8]1[CH2:47][CH2:46][C:11]2[N:12]=[C:13]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:45])=[CH:29][N:30]4[S:35]([C:38]3[CH:44]=[CH:43][C:41]([CH3:42])=[CH:40][CH:39]=3)(=[O:37])=[O:36])[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][N:19]([C:22](=[O:24])[CH3:23])[CH2:18][C@H:17]3[CH3:25])[C:10]=2[CH2:9]1)C1C=CC=CC=1.C(O)(=O)C.C1COCC1>[OH-].[OH-].[Pd+2].[C].O>[CH3:25][C@H:17]1[N:16]([C:15]2[C:10]3[CH2:9][NH:8][CH2:47][CH2:46][C:11]=3[N:12]=[C:13]([C:26]3[CH:34]=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:45])=[CH:29][N:30]4[S:35]([C:38]3[CH:44]=[CH:43][C:41]([CH3:42])=[CH:40][CH:39]=3)(=[O:36])=[O:37])[N:14]=2)[CH2:21][CH2:20][N:19]([C:22](=[O:24])[CH3:23])[CH2:18]1

Participants

6

Reactant 3

HCID 176Acetic AcidHCID 8028TetrahydrofuranHCID 71244807(R)-1-(4-(6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

Product 1

HCID 71240570(R)-1-(3-methyl-4-(2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)piperazin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 178502593HCID 178502593, compoundCatalystHCID 962WaterSolvent

Procedure

A mixture of (R)-1-(4-(6-benzyl-2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone (0.35 g, 0.539 mmol), acetic acid (0.154 mL, 2.70 mmol), THF (9 mL) and H2O (3 mL) was degassed via vacuum and recharged with nitrogen gas (2×). Then 20 mol % Pd(OH)2/carbon (0.114 g, 0.162 mmol) was added and the mixture was degassed via vacuum and placed under an atmosphere of hydrogen. The mixture was stirred at rt under H2 atmosphere via balloon for 2 h and then filtered. The solution was then diluted with EtOAc and washed with sat aq NaHCO3. The organic layer was washed with brine, dried over Na2SO4, filtered and concentrated to provide (R)-1-(3-methyl-4-(2-(3-methyl-1-tosyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)piperazin-1-yl)ethanone, which was used without the need for further purification. MS (ESI+) m/z 559.3 (M+H)+.

Workup

  1. customwas degassed via vacuum
  2. customthe mixture was degassed via vacuum
  3. filtrationfiltered
  4. additionThe solution was then diluted with EtOAc
  5. washwashed with sat aq NaHCO3
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-4e583253ff8149898f186cb986def674
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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