Sodium Carbonate → (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

HRID 80781Notes

Reaction equation

HRID 80781 reaction equation
[CH2:1]([N:8]1[CH2:28][CH2:27][C:11]2[N:12]=[C:13](Cl)[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)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:29][C:30]1[C:38]2[C:33](=[CH:34][CH:35]=[CH:36][C:37]=2B2OC(C)(C)C(C)(C)O2)[N:32]([S:48]([C:51]2[CH:57]=[CH:56][C:54]([CH3:55])=[CH:53][CH:52]=2)(=[O:50])=[O:49])[CH:31]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[CH2:1]([N:8]1[CH2:28][CH2:27][C:11]2[N:12]=[C:13]([C:37]3[CH:36]=[CH:35][CH:34]=[C:33]4[C:38]=3[C:30]([CH3:29])=[CH:31][N:32]4[S:48]([C:51]3[CH:57]=[CH:56][C:54]([CH3:55])=[CH:53][CH:52]=3)(=[O:50])=[O:49])[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)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 712404273-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indoleHCID 86690255(R)-1-(4-(6-benzyl-2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (R)-1-(4-(6-benzyl-2-chloro-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-4-yl)-3-methylpiperazin-1-yl)ethanone (0.27 g, 0.675 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole (0.305 g, 0.743 mmol) and 2 M aq Na2CO3 (1.1 mL, 2.19 mmol) in DME (3 mL) was degassed by sparging with argon. Pd(PPh3P)4 (0.117 g, 0.101 mmol) was then added and the mixture was heated in a microwave reactor at 140° C. for 1.5 h. The reaction was filtered and diluted with EtOAc, washed successively with sat aq Na2CO3 and, brine, and then dried over Na2SO4. After concentration the residue was purified by FCC (5-70% EtOAc/heptane) to provide (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. MS (ESI+) m/z 649.3 (M+H)+.

Workup

  1. customwas degassed
  2. customby sparging with argon
  3. filtrationThe reaction was filtered
  4. additiondiluted with EtOAc
  5. washwashed successively with sat aq Na2CO3 and, brine
  6. dry with materialdried over Na2SO4
  7. concentrationAfter concentration the residue
  8. customwas purified by FCC (5-70% EtOAc/heptane)

Sources & evidence

ORD record
ord-e9812e044d95419bb8b65a6b82425f08
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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