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

HRID 387330Notes

Reaction equation

HRID 387330 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]([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>[CH3:5][C:14]([O:41][CH2:38][CH2:6][N:7]([CH2:35][C:32]1[S:33][CH:34]=[C:30]([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][S:17](=[O:21])(=[O:20])[CH2:16][CH2:15]2)[CH:31]=1)[CH3:8])([CH3:19])[CH3:15]

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 593328005-(5-{[{2-[(1,1-Dimethylethyl)oxy]ethyl}(methyl)amino]methyl}-3-thienyl)-3-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-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 at 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 -[(1,1-dimethylethyl)oxy]ethyl}methylamine (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 (15 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 -[(1,1-dimethylethyl)oxy]ethyl}methylamine (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-f361bcc49e5a415fa6cc431b8ad76b37
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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