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

HRID 80784Notes

Reaction equation

HRID 80784 reaction equation
[CH3:1][C@H:2]1[N:7]([C:8]2[C:9]3[CH2:37][N:36]([C:38]4[CH:43]=[C:42]([C:44]5([CH3:48])[CH2:47][O:46][CH2:45]5)[CH:41]=[CH:40][C:39]=4[CH3:49])[CH2:35][CH2:34][C:10]=3[N:11]=[C:12]([C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH3:33])=[CH:17][N:18]4S(C3C=CC(C)=CC=3)(=O)=O)[N:13]=2)[CH2:6][CH2:5][N:4]([C:50](=[O:52])[CH3:51])[CH2:3]1.[OH-].[NH4+].[OH-].[K+]>CCO>[CH3:1][C@H:2]1[N:7]([C:8]2[C:9]3[CH2:37][N:36]([C:38]4[CH:43]=[C:42]([C:44]5([CH3:48])[CH2:45][O:46][CH2:47]5)[CH:41]=[CH:40][C:39]=4[CH3:49])[CH2:35][CH2:34][C:10]=3[N:11]=[C:12]([C:14]3[CH:22]=[CH:21][CH:20]=[C:19]4[C:15]=3[C:16]([CH3:33])=[CH:17][NH:18]4)[N:13]=2)[CH2:6][CH2:5][N:4]([C:50](=[O:52])[CH3:51])[CH2:3]1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 14923Ammonium HydroxideHCID 86690256(R)-1-(3-methyl-4-(2-(3-methyl-1-tosyl-1H-indol-4-yl)-6-(2-methyl-5-(3-methyloxetan-3-yl)phenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)piperazin-1-yl)ethanone

Product 1

HCID 71240647(R)-1-(3-methyl-4-(2-(3-methyl-1H-indol-4-yl)-6-(2-methyl-5-(3-methyloxetan-3-yl)phenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)piperazin-1-yl)ethanone

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of (R)-1-(3-methyl-4-(2-(3-methyl-1-tosyl-1H-indol-4-yl)-6-(2-methyl-5-(3-methyloxetan-3-yl)phenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)piperazin-1-yl)ethanone (0.104 g, 0.145 mmol), 30% ammonium hydroxide (0.854 mL, 21.70 mmol) and KOH (0.073 g, 1.302 mmol) in EtOH (4 mL) was heated in a microwave reactor at 100° C. for 30 min. The mixture was concentrated and partially purified by FCC (0-6% MeOH in DCM). Further purification with HPLC (C18, 15-85% CH3CN in H2O with 0.1% NH4OH) provided (R)-1-(3-methyl-4-(2-(3-methyl-1H-indol-4-yl)-6-(2-methyl-5-(3-methyloxetan-3-yl)phenyl)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)piperazin-1-yl)ethanone. 1H NMR (400 MHz, DMSO-d6 at 120° C.) δ ppm 10.50 (br. s., 1 H) 7.42 (d, J=8.08 Hz, 1 H) 7.25 (d, J=7.20 Hz, 1 H) 7.19 (d, J=7.83 Hz, 1 H) 7.07-7.15 (m, 2 H) 6.97 (s, 1 H) 6.90 (d, J=7.96 Hz, 1 H) 4.79 (d, J=5.43 Hz, 2 H) 4.53 (d, J=5.05 Hz, 2 H) 4.05-4.19 (m, 3 H) 3.91 (br. s., 1 H) 3.75 (br. s., 1 H) 3.56 (d, J=13.26 Hz, 1 H) 3.22-3.48 (m, 5 H) 3.00 (t, J=5.62 Hz, 2 H) 2.29 (s, 3 H) 2.07 (s, 3 H) 1.99-2.04 (m, 3 H) 1.65 (s, 3 H) 1.17 (d, J=6.44 Hz, 3 H); MS (ESI+) m/z 565.4 (M+H)+.

Workup

  1. concentrationThe mixture was concentrated
  2. custompartially purified by FCC (0-6% MeOH in DCM)
  3. customFurther purification with HPLC (C18, 15-85% CH3CN in H2O with 0.1% NH4OH)

Sources & evidence

ORD record
ord-c6016c011ecc4d5fbd3b44f8c34232e2
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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