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

HRID 80839Notes

Reaction equation

HRID 80839 reaction equation
C([N:8]1[CH2:48][CH2:47][C:11]2[N:12]=[C:13]([C:26]3[C:34]([CH3:35])=[CH:33][CH:32]=[C:31]4[C:27]=3[C:28]([CH3:46])=[N:29][N:30]4[S:36]([C:39]3[CH:45]=[CH:44][C:42]([CH3:43])=[CH:41][CH:40]=3)(=[O:38])=[O:37])[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][C@@H:19]([O:22][CH3:23])[C:18]([CH3:25])([CH3:24])[CH2:17]3)[C:10]=2[CH2:9]1)C1C=CC=CC=1.C(O)(=O)C>C1COCC1.O.[OH-].[OH-].[Pd+2]>[CH3:46][C:28]1[C:27]2[C:31](=[CH:32][CH:33]=[C:34]([CH3:35])[C:26]=2[C:13]2[N:14]=[C:15]([N:16]3[CH2:21][CH2:20][C@@H:19]([O:22][CH3:23])[C:18]([CH3:25])([CH3:24])[CH2:17]3)[C:10]3[CH2:9][NH:8][CH2:48][CH2:47][C:11]=3[N:12]=2)[N:30]([S:36]([C:39]2[CH:45]=[CH:44][C:42]([CH3:43])=[CH:41][CH:40]=2)(=[O:37])=[O:38])[N:29]=1

Participants

6

Reactant 2

HCID 176Acetic AcidHCID 71244815(R)-6-Benzyl-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Product 1

HCID 71239021(R)-2-(3,5-Dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 3

HCID 9942167Palladium hydroxideCatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
40 °C

Procedure

To a solution of (R)-6-benzyl-2-(3,5-dimethyl-1-tosyl-1H-indazol-4-yl)-4-(4-methoxy-3,3-dimethylpiperidin-1-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidine (3.0 g, 4.51 mmol) in THF (24 mL) and water (6 mL) was added acetic acid (1.30 mL, 22.6 mmol). The solution was warmed to 40° C. and Pd(OH)2 20% on carbon (0.792 mg, 1.13 mmol) was added. The mixture was then stirred under a hydrogen atmosphere for 2.25 h. The mixture was then allowed to cool to rt and was filtered over Celite®, washing with EtOAc and MeOH. The filtrate was then basified with aqueous 1 N NaOH and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated under reduce pressure. The residue was then purified via FCC (0-15% MeOH/DCM; with 10% NH4OH in DCM) to obtain the title compound. MS (ESI+) m/z 575.5 (M+H)+.

Workup

  1. temperatureto cool to rt
  2. filtrationwas filtered over Celite®
  3. washwashing with EtOAc and MeOH
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was then purified via FCC (0-15% MeOH/DCM; with 10% NH4OH in DCM)

Sources & evidence

ORD record
ord-1f026192e20d406aaf0f940cf687c0ac
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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