Water → 3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-{5-[(methyloxy)methyl]-2-thienyl}-1H-indole-7-carboxamide

HRID 387350Notes

Reaction equation

HRID 387350 reaction equation
Br[C:2]1[S:3][C:4]([CH2:7][O:8][CH3:9])=[CH:5][CH:6]=1.[O:10]=[S:11]1(=[O:38])[CH2:16][CH2:15][CH:14]([C:17]2[C:25]3[C:20](=[C:21]([C:35]([NH2:37])=[O:36])[CH:22]=[C:23](B4OC(C)(C)C(C)(C)O4)[CH:24]=3)[NH:19][CH:18]=2)[CH2:13][CH2:12]1.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]>[O:38]=[S:11]1(=[O:10])[CH2:16][CH2:15][CH:14]([C:17]2[C:25]3[C:20](=[C:21]([C:35]([NH2:37])=[O:36])[CH:22]=[C:23]([C:2]4[S:3][C:4]([CH2:7][O:8][CH3:9])=[CH:5][CH:6]=4)[CH:24]=3)[NH:19][CH:18]=2)[CH2:13][CH2:12]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 13025550HCID 13025550, compoundHCID 593327113-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide

Product 1

HCID 593325863-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-{5-[(methyloxy)methyl]-2-thienyl}-1H-indole-7-carboxamideYield 43%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

2-Bromo-5-[(methyloxy)methyl]thiophene (35 mg, 0.16 mmol), 3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamide (55 mg, 0.13 mmol) and K2CO3 (83 mg, 0.14 mmol) was taken up in 1,4-dioxane (3 mL) and water (1.5 mL) in a microwave vial. The mixture was degassed by bubbling argon through it for 5 min. PdCl2(dppf) (17 mg, 0.023 mmol) was added, and the reaction was heated in a microwave for 5 min at 100° C. The reaction mixture was concentrated, diluted in DMSO, and purified on a Gilson HPLC(NH4OH buffer), giving 18.2 mg (43%) of the title compound.

Workup

  1. customThe mixture was degassed
  2. customby bubbling argon through it for 5 min
  3. concentrationThe reaction mixture was concentrated
  4. additiondiluted in DMSO
  5. custompurified on a Gilson HPLC(NH4OH buffer)

Sources & evidence

ORD record
ord-d42f33e6552648908e837b86bd67ea6e
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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