Potassium Phosphate, Tribasic → methyl 3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indole-5-carboxylate

HRID 634187Notes

Reaction equation

HRID 634187 reaction equation
CC1(C)C(C)(C)OB([C:9]2[C:17]3[C:12](=[CH:13][CH:14]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=3)[N:11]([S:22]([C:25]3[CH:31]=[CH:30][C:28]([CH3:29])=[CH:27][CH:26]=3)(=[O:24])=[O:23])[CH:10]=2)O1.Br[C:34]1[CH:39]=[N:38][CH:37]=[C:36]([CH:40]2[CH2:42][CH2:41]2)[N:35]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1>[CH:40]1([C:36]2[N:35]=[C:34]([C:9]3[C:17]4[C:12](=[CH:13][CH:14]=[C:15]([C:18]([O:20][CH3:21])=[O:19])[CH:16]=4)[N:11]([S:22]([C:25]4[CH:26]=[CH:27][C:28]([CH3:29])=[CH:30][CH:31]=4)(=[O:24])=[O:23])[CH:10]=3)[CH:39]=[N:38][CH:37]=2)[CH2:42][CH2:41]1

Participants

9

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 457883052-Bromo-6-cyclopropylpyrazine2×HCID 68328028methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate

Product 1

HCID 86725108methyl 3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indole-5-carboxylateYield 97.3%

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A brown mixture of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-tosyl-1H-indole-5-carboxylate (2.32 g, 5.10 mmol), 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalysts, Inc., Princeton, N.J.; 1.116 g, 5.60 mmol), Pd2(dba)3 (0.140 g, 0.153 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (XPhos; 0.146 g, 0.306 mmol), and potassium phosphate (3.24 g, 15.29 mmol) in a mixture of dioxane (45 mL) and H2O (4.50 mL) was sparged with argon then heated at 100° C. for 3 h. Additional 2-bromo-6-cyclopropylpyrazine (CombiPhos Catalysts, Inc., Princeton, N.J.; 550 mg, 2.80 mmol) was added, and the resulting mixture was stirred at 100° C. for 2 h. The reaction was cooled to RT, diluted with DCM (50 mL), and concentrated onto silica gel. Chromatographic purification (silica gel, 0-80% EtOAc/Hex) furnished methyl 3-(6-cyclopropylpyrazin-2-yl)-1-tosyl-1H-indole-5-carboxylate (2.22 g, 4.96 mmol, 97%) as a light-yellow solid: MS (ESI, pos. ion) m/z: 448.1 (M+1).

Workup

  1. customwas sparged with argon
  2. temperatureThe reaction was cooled to RT
  3. concentrationconcentrated onto silica gel
  4. customChromatographic purification (silica gel, 0-80% EtOAc/Hex)

Sources & evidence

ORD record
ord-016801001d5542779bd07970ad066571
Source dataset
uspto-grants-2016_04
Patent number
US09321756B2

Reaction notes

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