Potassium Carbonate → 5-[6-(Dimethylamino)-3-pyridinyl]-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

HRID 656082Notes

Reaction equation

HRID 656082 reaction equation
[CH3:1][N:2]([CH3:12])[C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.Br[C:14]1[CH:15]=[C:16]2[C:20](=[C:21]([C:23]([NH2:25])=[O:24])[CH:22]=1)[NH:19][CH:18]=[C:17]2[CH:26]1[CH2:31][CH2:30][S:29](=[O:33])(=[O:32])[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O>[CH3:1][N:2]([CH3:12])[C:3]1[N:8]=[CH:7][C:6]([C:14]2[CH:15]=[C:16]3[C:20](=[C:21]([C:23]([NH2:25])=[O:24])[CH:22]=2)[NH:19][CH:18]=[C:17]3[CH:26]2[CH2:27][CH2:28][S:29](=[O:32])(=[O:33])[CH2:30][CH2:31]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 27632716-(Dimethylamino)pyridine-3-boronic acidHCID 593327575-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

Product 1

HCID 593327015-[6-(Dimethylamino)-3-pyridinyl]-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamideYield 34.8%

Reagents, catalysts & solvents 1

HCID 218864351,4-Dioxane--water (1/1)Solvent

Conditions

Temperature
150 °C

Procedure

[6-(Dimethylamino)-3-pyridinyl]boronic acid (34 mg, 0.202 mmol), 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (75 mg, 0.202 mmol) and potassium carbonate (84 mg, 0.606 mmol) were suspended in 4 mL of dioxane:water (3:1) and degassed for a few minutes with nitrogen gas. Pd(PPh3)4 (23 mg) was then added and the reaction mixture was heated in a microwave oven at 150° C. for 40 minutes on ‘high’ absorption setting. After heating, LCMS of all crude reaction mixtures showed the desired m/z with few impurities. The crude reaction mixtures were filtered through 500 mg Stratospheres SPE Thiol cartridges eluting with 10 mL methanol/DCM (1:1) and concentrated. The residues were dissolved in DMSO (˜3 mL) and purified via RP-HPLC using an XBridge Prep C18 column with water/acetonitrile (0.1% NH4OH buffer). The desired fractions were concentrated, giving 0.029 g (34.8%) of the title compound.

Workup

  1. customdegassed for a few minutes with nitrogen gas
  2. additionPd(PPh3)4 (23 mg) was then added
  3. customabsorption
  4. temperatureAfter heating
  5. customLCMS of all crude reaction mixtures
  6. customThe crude reaction mixtures
  7. filtrationwere filtered through 500 mg Stratospheres SPE Thiol cartridges
  8. washeluting with 10 mL methanol/DCM (1:1)
  9. concentrationconcentrated
  10. dissolutionThe residues were dissolved in DMSO (˜3 mL)
  11. custompurified via RP-HPLC
  12. concentrationThe desired fractions were concentrated

Sources & evidence

ORD record
ord-dd9f812407de4c0f95bbf91ca5ec64b0
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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