Sodium Carbonate → (S)-methyl 2-(1-(tert-butoxycarbonyl)-1H-indazol-5-yl)-3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)quinoxaline-6-carboxylate

HRID 1403513

Reaction equation

HRID 1403513 reaction equation
[CH3:1][C@H:2]1[CH2:7][N:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=2)[CH2:5][CH2:4][N:3]1[C:14]1[C:15](OS(C(F)(F)F)(=O)=O)=[N:16][C:17]2[C:22]([N:23]=1)=[CH:21][C:20]([C:24]([O:26][CH3:27])=[O:25])=[CH:19][CH:18]=2.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)OB([C:48]2[CH:49]=[C:50]3[C:54](=[CH:55][CH:56]=2)[N:53]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[N:52]=[CH:51]3)OC1(C)C>COCCOC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:60]([O:59][C:57]([N:53]1[C:54]2[C:50](=[CH:49][C:48]([C:15]3[C:14]([N:3]4[CH2:4][CH2:5][N:6]([C:8]5[CH:13]=[CH:12][CH:11]=[CH:10][N:9]=5)[CH2:7][C@@H:2]4[CH3:1])=[N:23][C:22]4[C:17](=[CH:18][CH:19]=[C:20]([C:24]([O:26][CH3:27])=[O:25])[CH:21]=4)[N:16]=3)=[CH:56][CH:55]=2)[CH:51]=[N:52]1)=[O:58])([CH3:63])([CH3:61])[CH3:62]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 18525862tert-Butyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylateHCID 86670573(S)-methyl 3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate

Product 1

HCID 70665358(S)-methyl 2-(1-(tert-butoxycarbonyl)-1H-indazol-5-yl)-3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)quinoxaline-6-carboxylateYield 60.8%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of (S)-methyl 3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)-2-(trifluoromethylsulfonyloxy)quinoxaline-6-carboxylate (240 mg, 0.38 mmol) in ethylene glycol dimethyl ether (20 ml) was added Pd(PPh3)4 (27 mg, 0.02 mmol), sodium carbonate (74.3 mg, 0.69 mmol) in water (6 ml), and tert-butyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate (300 mg, 0.87 mmol). After stirring 90 minutes at 90° C. in an oil bath, the reaction was then quenched by the addition of water (200 ml), extracted with dichloromethane (3×30 ml), dried over anhydrous magnesium sulfate and concentrated under vacuum to afford a residue, which was purified via silica gel chromatography (20% ethyl acetate in petroleum ether) to afford (S)-methyl 2-(1-(tert-butoxycarbonyl)-1H-indazol-5-yl)-3-(2-methyl-4-(pyridin-2-yl)piperazin-1-yl)quinoxaline-6-carboxylate as a yellow solid (134 mg, 60%).

Workup

  1. customthe reaction was then quenched by the addition of water (200 ml)
  2. extractionextracted with dichloromethane (3×30 ml)
  3. dry with materialdried over anhydrous magnesium sulfate
  4. concentrationconcentrated under vacuum
  5. customto afford a residue, which
  6. customwas purified via silica gel chromatography (20% ethyl acetate in petroleum ether)

Sources & evidence

ORD record
ord-049a0f96a5c44bcc8258a86593979ea9
Source dataset
uspto-grants-2014_12
Patent number
US08912188B2

Linked notes

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