Potassium Hydroxide → (R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

HRID 80779Notes

Reaction equation

HRID 80779 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][N:21]([C:24](=[O:26])[CH3:25])[CH2:20][C@H:19]4[CH3:27])[C:12]=3[CH2:11]2)[CH:9]=1)([CH3:3])[CH3:2].[NH4+].[OH-].[OH-].[K+]>CCO.CCOC(C)=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][N:21]([C:24](=[O:26])[CH3:25])[CH2:20][C@H:19]4[CH3:27])[C:12]=3[CH2:11]2)[CH:9]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 71240550(R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-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 71240609(R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

(R)-1-(4-(6-(5-Isopropyl-2-methylphenyl)-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 was dissolved in EtOH (2 mL), then NH4OH (0.54 mL, 13.7 mmol) was added followed by KOH (46 mg, 0.821 mmol). The mixture was heated in a microwave reactor at 100° C. for 1 h. The reaction was then diluted with EtOAc and washed with brine. After concentration, the resulting residue was purified by HPLC (C18, 15-85% acetonitrile in H2O with 0.1% NH4OH) to provide (R)-1-(4-(6-(5-isopropyl-2-methylphenyl)-2-(3-methyl-1H-indol-4-yl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone. 1H NMR (400 MHz, CD3CN) δ ppm 9.15 (br. s., 1 H) 7.46 (d, J=8.08 Hz, 1 H) 7.26 (d, J=7.33 Hz, 1 H) 7.16 (dd, J=16.29, 7.96 Hz, 2 H) 7.06 (d, J=13.64 Hz, 2 H) 6.91 (dd, J=7.58, 1.52 Hz, 1 H) 3.98-4.16 (m, 4 H) 3.46-3.67 (m, 2 H) 3.26-3.46 (m, 4 H) 2.84-3.13 (m, 4 H) 2.26 (s, 3 H) 2.00-2.06 (m, 6 H) 1.23 (d, J=6.82 Hz, 6H) 1.11-1.21 (m, 3 H); MS (ESI+) m/z 537.4 (M+H)+.

Workup

  1. washwashed with brine
  2. concentrationAfter concentration
  3. customthe resulting residue was purified by HPLC (C18, 15-85% acetonitrile in H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-c585db33047546409ab002740707d358
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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