Potassium Carbonate → 3-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-{[ethyl(methyl)amino]methyl}-3-thienyl)-1H-indole-7-carboxamide

HRID 656090Notes

Reaction equation

HRID 656090 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)[S:33][CH:34]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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: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]([CH2:35][N:7]([CH2:6][CH3:5])[CH3:8])[S:33][CH:34]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:15][CH2:16]1

Participants

7

Reactant 3

HCID 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 593325713-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-(5-{[ethyl(methyl)amino]methyl}-3-thienyl)-1H-indole-7-carboxamideYield 5.4%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (400 mg, 1.08 mmol) in dioxane and water (4 mL/1 mL) was added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thiophenecarbaldehyde (462 mg, 1.94 mmol), Pd(PPh3)4 (100 mg) and K2CO3 (447 mg, 3.24 mmol). The reaction mixture was heated to 150° C. for 20 minutes by microwave irradiation. The organic phase was concentrated and redissolved in DMSO (10 mL). The resulting solution was split to eight. NaBH3CN (30 mg), ZnCl2 (30 mg) and methyl ethylamine (50 mg) were added. The mixture was heated at 100° C. for 30 minutes which was then filtered and purified by HPLC with TFA to afford the title compound (13 mg).

Workup

  1. concentrationThe organic phase was concentrated
  2. dissolutionredissolved in DMSO (10 mL)
  3. customThe resulting solution was split to eight
  4. additionNaBH3CN (30 mg), ZnCl2 (30 mg) and methyl ethylamine (50 mg) were added
  5. temperatureThe mixture was heated at 100° C. for 30 minutes which
  6. filtrationwas then filtered
  7. custompurified by HPLC with TFA

Sources & evidence

ORD record
ord-e1fa6193b893453d83066e6a0e658727
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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