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

HRID 387339Notes

Reaction equation

HRID 387339 reaction equation
[O:1]=[S:2]1(=[O:29])[CH2:7][CH2:6][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=[C:14](B4OC(C)(C)C(C)(C)O4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Br[C:37]1[CH:38]=[C:39]([CH2:42][CH2:43][CH2:44][OH:45])[S:40][CH:41]=1.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:29]=[S:2]1(=[O:1])[CH2:3][CH2:4][CH:5]([C:8]2[C:16]3[C:11](=[C:12]([C:26]([NH2:28])=[O:27])[CH:13]=[C:14]([C:37]4[CH:38]=[C:39]([CH2:42][CH2:43][CH2:44][OH:45])[S:40][CH:41]=4)[CH:15]=3)[NH:10][CH:9]=2)[CH2:6][CH2:7]1

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 593327113-(1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-7-carboxamideHCID 626030043-(4-Bromothiophen-2-yl)propan-1-ol

Product 1

HCID 593325783-(1,1-Dioxidotetrahydro-2H-thiopyran-4-yl)-5-[5-(3-hydroxypropyl)-3-thienyl]-1H-indole-7-carboxamideYield 41%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

In a 5 mL microwave vial was added 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, 0.131 mmol), PdCl2(dppf)-CH2Cl2 adduct (17.18 mg, 0.021 mmol), and K2CO3 (83 mg, 0.601 mmol). Then 3-(4-bromo-2-thienyl)-1-propanol (37.8 mg, 0.171 mmol) in 1,4-dioxane (3 mL) was added to give an orange solution. Water (1.5 mL) was added and the solution was heated to 100° C. at high power in the microwave for 5 min, cooled. The reaction was filtered through a thiol paladium extraction column. The column was washed with CH2Cl2 and the combined filtrates were concentrated and purified on a Gilson HPLC(NH4OH buffer), giving 23 mg (41%) of the title compound.

Workup

  1. customto give an orange solution
  2. temperaturecooled
  3. filtrationThe reaction was filtered through a thiol paladium extraction column
  4. washThe column was washed with CH2Cl2
  5. concentrationthe combined filtrates were concentrated
  6. custompurified on a Gilson HPLC(NH4OH buffer)

Sources & evidence

ORD record
ord-627eaf937074413e876c347f9594664e
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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