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

HRID 656087Notes

Reaction equation

HRID 656087 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:38]([O-:41])([O-])=O.[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[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]([CH3:8])[CH2:6][CH2:5][O:41][CH3:38])[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 593327813-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-[5-({methyl[2-(methyloxy)ethyl]amino}methyl)-3-thienyl]-1H-indole-7-carboxamideYield 14%

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
150 °C

Procedure

To 5-bromo-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (100 mg, 0.27 mmol) in dioxane and water (3 mL/1 mL) were added 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thiophenecarbaldehyde (116 mg), Pd(PPH3)4 (30 mg) and K2CO3 (112 mg). The reaction mixture was heated to 150° C. for 900 seconds in microwave. The organic phase was separated, concentrated, and redissolved in DMSO (3 mL). The resulting solution was split to two. NaBH3CN (30 mg), ZnCl2 (30 mg) and N-methyl-2-(methyloxy)ethanamine (50 mg) were added. The mixture was heated to 100° C. for 30 minutes in microwave which was then purified by HPLC with TFA to afford the title compound (9 mg).

Workup

  1. customThe organic phase was separated
  2. concentrationconcentrated
  3. dissolutionredissolved in DMSO (3 mL)
  4. customThe resulting solution was split to two
  5. additionNaBH3CN (30 mg), ZnCl2 (30 mg) and N-methyl-2-(methyloxy)ethanamine (50 mg) were added
  6. temperatureThe mixture was heated to 100° C. for 30 minutes in microwave which
  7. customwas then purified by HPLC with TFA

Sources & evidence

ORD record
ord-cfe9b60d04d84b049ffa071ff7a2e146
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

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