Water → 3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide

HRID 387324Notes

Reaction equation

HRID 387324 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][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]1.CC1(C)C(C)(C)OB([C:30]2[CH:31]=[C:32]([CH:35]=[O:36])[S:33][CH:34]=2)O1.C(=O)([O-])[O-].[K+].[K+].O>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].C(Cl)Cl>[O:20]=[S:17]1(=[O:21])[CH2:18][CH2:19][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:30]4[CH:31]=[C:32]([CH:35]=[O:36])[S:33][CH:34]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH2:16]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 467397834-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carbaldehydeHCID 593327575-Bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide

Product 1

HCID 593325693-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-formyl-3-thienyl)-1H-indole-7-carboxamide

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
10 °C

Procedure

5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (150 mg, 0:4 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thiophenecarbaldehyde (115 mg, 0.48 mmol, 1.2 eq), PdCl2(dppf)-CH2Cl2 adduct (29 mg, 0.04 mmol, 0.09 eq), and potassium carbonate (170 mg, 1.2 mmol, 3 eq) were diluted in dioxane (3 mL) and water (1.5 mL) in a 2-5 mL microwave tube. The mixture was degassed by bubbling argon through for 5 minutes, then the reaction was heated in a microwave oven under regular absorption at 10° C. for 5 minutes. The reaction mixture was filtered through a thiol SPE cartridge, washing well with acetone, and the solvent was removed in vacuo. The crude residue was triturated from diethyl ether to give a pink solid. Minor impurities were present, but this material was suitable for use in the reductive amination step as is (210 mg, 0.52 mmol, 129%).

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon through for 5 minutes
  3. filtrationThe reaction mixture was filtered through a thiol SPE cartridge
  4. washwashing well with acetone
  5. customthe solvent was removed in vacuo
  6. customThe crude residue was triturated from diethyl ether
  7. customto give a pink solid

Sources & evidence

ORD record
ord-44aad11a2a3e4713a9592c3d1ded5f66
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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