Potassium Carbonate → 4-[2-chloro-4-(1H-indol-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

HRID 2405378Notes

Reaction equation

HRID 2405378 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:12]([CH2:13][C@@H:14]3[CH2:18][CH2:17][N:16]([C:19]([CH:21]4[CH2:23][CH2:22]4)=[O:20])[CH2:15]3)=[N:11][NH:10][C:9]2=[O:24])=[C:4]([Cl:25])[CH:3]=1.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]3[C:40](=[CH:41][CH:42]=2)[NH:39][CH:38]=[CH:37]3)O1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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>[Cl:25][C:4]1[CH:3]=[C:2]([C:34]2[CH:35]=[C:36]3[C:40](=[CH:41][CH:42]=2)[NH:39][CH:38]=[CH:37]3)[CH:7]=[CH:6][C:5]=1[N:8]1[C:12]([CH2:13][C@@H:14]2[CH2:18][CH2:17][N:16]([C:19]([CH:21]3[CH2:23][CH2:22]3)=[O:20])[CH2:15]2)=[N:11][NH:10][C:9]1=[O:24]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 27347725-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indoleHCID 673771034-(4-bromo-2-chlorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one

Product 1

HCID 673764944-[2-chloro-4-(1H-indol-5-yl)phenyl]-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-oneYield 48%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 4-(4-bromo-2-chlorophenyl)-5-{[(3S)-1-(cyclopropylcarbonyl)-3-pyrrolidinyl]methyl}-2,4-dihydro-3H-1,2,4-triazol-3-one (140 mg, 0.329 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole (80 mg, 0.329 mmol), potassium carbonate (182 mg, 1.315 mmol), and tetrakis(triphenylphosphine)palladium(0) (19.0 mg, 0.016 mmol) in 1,4-dioxane (5 mL) and water (2 mL) was heated at 120° C. for 3.5 hr. The reaction mixture was cooled and loaded onto a silica gel pre-column and purified by flash chromatography (dichloromethane to 6% methanol in dichloromethane) to afford the title product (73 mg, 0.158 mmol, 48% yield). 1H NMR (400 MHz, CDCl3) δ ppm 8.96-8.78 (m, 1H), 8.37 (br. s, 1H), 7.92-7.82 (m, 2H), 7.76-7.64 (m, 1H), 7.56-7.47 (m, 1H), 7.47-7.39 (m, 2H), 7.36-7.30 (m, 1H), 6.76-6.61 (m, 1H), 4.04-3.02 (m, 4H), 2.80-2.39 (m, 3H), 2.34-2.03 (m, 1H), 1.84-1.60 (m, 1H), 1.07-0.94 (m, 2H), 0.76 (dd, J=3.3, 7.8 Hz, 2H).

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompurified by flash chromatography (dichloromethane to 6% methanol in dichloromethane)

Sources & evidence

ORD record
ord-3239436b081d4d0aaeb83dfcdf82809e
Source dataset
uspto-grants-2014_08
Patent number
US08802864B2

Reaction notes

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