Potassium Carbonate → 5-(5-formyl-3-thienyl)-3-(1-{[3-(methyloxy)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamide

HRID 2267508Notes

Reaction equation

HRID 2267508 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=1)[NH:7][CH:6]=[C:5]2[CH:14]1[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])(=[O:22])=[O:21])[CH2:16][CH2:15]1.O1CCOCC1.CC1(C)C(C)(C)OB([C:42]2[CH:43]=[C:44]([CH:47]=[O:48])[S:45][CH:46]=2)O1.C(=O)([O-])[O-].[K+].[K+]>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.O>[CH:47]([C:44]1[S:45][CH:46]=[C:42]([C:2]2[CH:3]=[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=2)[NH:7][CH:6]=[C:5]3[CH:14]2[CH2:19][CH2:18][N:17]([S:20]([CH2:23][CH2:24][CH2:25][O:26][CH3:27])(=[O:22])=[O:21])[CH2:16][CH2:15]2)[CH:43]=1)=[O:48]

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 467397834-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carbaldehydeHCID 590033305-bromo-3-(1-{[3-(methyloxy)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamide

Product 1

HCID 116201055-(5-formyl-3-thienyl)-3-(1-{[3-(methyloxy)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamideYield 61%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

To 5-bromo-3-(1-{[3-(methyloxy)propyl]sulfonyl}-4-piperidinyl)-1H-indole-7-carboxamide (170 mg, 0.37 mmol) in mixture of dioxane (4.5 mL) and water (1.5 mL), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thiophenecarbaldehyde (265.2 mg, 1.11 mmol), potassium carbonate (309 mg, 2.22 mmol) and Pd(PPh3)4 (44.2 mg, 0.04 mmol) were added. The reaction mixture was heated by microwave at 150° C. for 20 minutes. Then all the solvent was evaporated. The residue was partitioned between ethyl acetate (50 mL) and water (50 mL). The water layer was extracted with ethyl acetate (2×50 mL). The combined organic phase washed with brine (50 mL) and dried with Mg2SO4 and concentrated. The crude product was purified by Combiflash (dichloromethane/methanol, 1%-40% methanol, 25 min.) to give title compound (110 mg, 61%).

Workup

  1. additionwere added
  2. customThen all the solvent was evaporated
  3. customThe residue was partitioned between ethyl acetate (50 mL) and water (50 mL)
  4. extractionThe water layer was extracted with ethyl acetate (2×50 mL)
  5. washThe combined organic phase washed with brine (50 mL)
  6. dry with materialdried with Mg2SO4
  7. concentrationconcentrated
  8. customThe crude product was purified by Combiflash (dichloromethane/methanol, 1%-40% methanol, 25 min.)

Sources & evidence

ORD record
ord-58ce49aa251943da84ae716bf63c3ac2
Source dataset
uspto-grants-2010_12
Patent number
US07858796B2

Reaction notes

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