Cesium carbonate → (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

HRID 80783Notes

Reaction equation

HRID 80783 reaction equation
[CH3:1][C@H:2]1[N:7]([C:8]2[C:9]3[CH2:37][NH:36][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]4[S:23]([C:26]3[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=3)(=[O:25])=[O:24])[N:13]=2)[CH2:6][CH2:5][N:4]([C:38](=[O:40])[CH3:39])[CH2:3]1.FC(F)(F)S(O[C:47]1[CH:52]=[C:51]([C:53]2([CH3:57])[CH2:56][O:55][CH2:54]2)[CH:50]=[CH:49][C:48]=1[CH3:58])(=O)=O.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1>[CH3:1][C@H:2]1[N:7]([C:8]2[C:9]3[CH2:37][N:36]([C:49]4[CH:50]=[C:51]([C:53]5([CH3:57])[CH2:56][O:55][CH2:54]5)[CH:52]=[CH:47][C:48]=4[CH3:58])[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]4[S:23]([C:26]3[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=3)(=[O:24])=[O:25])[N:13]=2)[CH2:6][CH2:5][N:4]([C:38](=[O:40])[CH3:39])[CH2:3]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 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)ethanoneHCID 866902572-Methyl-5-(3-methyloxetan-3-yl)phenyl trifluoromethanesulfonate

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of (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 (0.155 g, 0.278 mmol), 2-methyl-5-(3-methyloxetan-3-yl)phenyl trifluoromethanesulfonate (0.086 g, 0.278 mmol) prepared as described in Example 13, cesium carbonate (0.272 g, 0.834 mmol) and chloro(2-dicyclohexylphosphino-2′-4′-6′-triisopropyl-1,1′-biphenyl)[2-(2-aminoethyl)phenyl]palladium(II)-methyl-t-butylether adduct (CAS#1028276-56-5) (0.031 g, 0.042 mmol) in THF (4 mL) was heated in a microwave reactor at 140° C. for 3 h. The reaction was then filtered and concentrated, the resulting residue was purified by FCC (60-100% EtOAc/DCM) to provide (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. MS (ESI+) m/z 719.3 (M+H)+.

Workup

  1. customprepared
  2. filtrationThe reaction was then filtered
  3. concentrationconcentrated
  4. customthe resulting residue was purified by FCC (60-100% EtOAc/DCM)

Sources & evidence

ORD record
ord-5155ea08b69e4d8e94f2a1d073e59ea1
Source dataset
uspto-grants-2014_09
Patent number
US08846656B2

Reaction notes

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