Potassium Carbonate → 5-(2-chloro-4-pyridinyl)-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

HRID 387322Notes

Reaction equation

HRID 387322 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](B(O)O)[CH:5]=[CH:4][N:3]=1.Br[C:12]1[CH:13]=[C:14]2[C:18](=[C:19]([C:21]([NH2:23])=[O:22])[CH:20]=1)[NH:17][CH:16]=[C:15]2[CH:24]1[CH2:29][CH2:28][S:27](=[O:31])(=[O:30])[CH2:26][CH2:25]1.C(=O)([O-])[O-].[K+].[K+].O1CCOCC1>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[Cl:1][C:2]1[CH:7]=[C:6]([C:12]2[CH:13]=[C:14]3[C:18](=[C:19]([C:21]([NH2:23])=[O:22])[CH:20]=2)[NH:17][CH:16]=[C:15]3[CH:24]2[CH2:25][CH2:26][S:27](=[O:30])(=[O:31])[CH2:28][CH2:29]2)[CH:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 51515952-Chloropyridine-4-boronic acidHCID 593327575-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

Product 1

HCID 593326655-(2-chloro-4-pyridinyl)-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamideYield 19.61%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (2-chloro-4-pyridinyl)boronic acid (0.095 g, 0.606 mmol), 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (0.075 g, 0.202 mmol) and potassium carbonate (0.168 g, 1.212 mmol) was added 1,4-dioxane (0.898 mL)/water (0.449 mL). The mixture was degassed with nitrogen and PdCl2(dppf) (0.015 g, 0.020 mmol) was added. The reaction mixture was heated in a microwave oven at 100° C. for 5 minutes on ‘high’ absorption setting. LCMS of crude reaction mixture shows the desired m/z and some unreacted starting material (very close ret. times). The reaction mixture was filtered through a Thiol SPE cartridge (500 mg) eluting with 1:1 MeOH/DCM (10 mL). The filtrate was purified with RP-HPLC (XBridge Column, 0.1% NH4OH). The fractions containing the desired compound are combined and concentrated to give 5-(2-chloro-4-pyridinyl)-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (0.016 g, 19.61%).

Workup

  1. additionwas added
  2. customabsorption
  3. customLCMS of crude reaction mixture
  4. filtrationThe reaction mixture was filtered through a Thiol SPE cartridge (500 mg)
  5. washeluting with 1:1 MeOH/DCM (10 mL)
  6. customThe filtrate was purified with RP-HPLC (XBridge Column, 0.1% NH4OH)
  7. additionThe fractions containing the desired compound
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b6a832b22fc04bcf8c311537705aeb1a
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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