Potassium Carbonate → HCID 59332756, compound

HRID 656139Notes

Reaction equation

HRID 656139 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])[C:16]([CH3:23])([CH3:22])[CH2:15]1.CC1(C)C(C)(C)OB([C:32]2[CH:33]=[C:34]([CH:37]=[O:38])[S:35][CH:36]=2)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O.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]>[CH3:22][C:16]1([CH3:23])[CH2:15][CH:14]([C:5]2[C:4]3[C:8](=[C:9]([C:11]([NH2:13])=[O:12])[CH:10]=[C:2]([C:32]4[CH:33]=[C:34]([CH:37]=[O:38])[S:35][CH:36]=4)[CH:3]=3)[NH:7][CH:6]=2)[CH2:19][CH2:18][S:17]1(=[O:21])=[O:20]

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 467397834-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carbaldehydeHCID 59332724HCID 59332724, compound

Product 1

HCID 59332756HCID 59332756, compoundYield 5.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

(racemic)-5-Bromo-3-(2,2-dimethyl-1,1-dioxidotetrahydro-2H-thiopyran-4-yl)-1H-indole-7-carboxamide (170 mg, 0.426 mmol) was placed in a microwave vial and dissolved in 1,4-dioxane (10 mL) and water (5 mL). 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-thiophenecarbaldehyde (203 mg, 0.851 mmol) and K2CO3 (177 mg, 1.277 mmol) was added. Argon was bubbled through the mixture for 10 min. PdCl2(dppf) (16.43 mg, 0.034 mmol) was added, and argon was bubbled another 10 mins. The vial was sealed and put under microwave 5 mins at 100° C. with high absorption parameter. The mixture was run through a thiol-SPE column eluting with MeOH. The fraction containing product (lcms) are combined and solvent was evaporated. One fraction of the residue was purified by Preparative HPLC. Conditions: aqueous phase contains 0.1% NH4OH (Ammonium Gilson) starting with 20% acetonitrile to finish with 80% acetonitrile in 60 min. The product stays around 17-18 mins in the column. The title product (10 mg) was obtained. The other fraction was purified by FlashChromatography (DCM 100% to DCM 30%/-DCM 90/MeOH 7/NH4OH aq 3-70% in 30 mins) to give 90 mg of the title compound.

Workup

  1. customArgon was bubbled through the mixture for 10 min
  2. customargon was bubbled another 10 mins
  3. customThe vial was sealed
  4. washeluting with MeOH
  5. additionThe fraction containing product (lcms)
  6. customsolvent was evaporated
  7. customOne fraction of the residue was purified by Preparative HPLC
  8. waitto finish with 80% acetonitrile in 60 min
  9. waitThe product stays around 17-18 mins in the column

Sources & evidence

ORD record
ord-ed5cb96fc2ef45bd914e3448f1cf3b2c
Source dataset
uspto-grants-2011_12
Patent number
US08071584B2

Reaction notes

Loading…