Potassium Carbonate → 1,1-dimethylethyl 5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate

HRID 1909941Notes

Reaction equation

HRID 1909941 reaction equation
Br[C:2]1[C:6]2[C:7]([NH2:11])=[N:8][CH:9]=[CH:10][C:5]=2[S:4][CH:3]=1.CC1(C)C(C)(C)OB([C:20]2[CH:21]=[C:22]3[C:26](=[CH:27][CH:28]=2)[N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24][CH2:23]3)O1.C(=O)([O-])[O-].[K+].[K+]>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.O1CCOCC1>[NH2:11][C:7]1[C:6]2[C:2]([C:20]3[CH:21]=[C:22]4[C:26](=[CH:27][CH:28]=3)[N:25]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:24][CH2:23]4)=[CH:3][S:4][C:5]=2[CH:10]=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 184507973-Bromothieno[3,2-c]pyridin-4-amineHCID 18451469tert-butyl 5-(tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate

Product 1

HCID 668238131,1-dimethylethyl 5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylateYield 115.8%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a 250 mL round bottom flask was added 3-bromothieno[3,2-c]pyridin-4-amine (2.65 g, 11.59 mmol), 1,1-dimethylethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (5 g, 14.48 mmol), 1,4-Dioxane (50 mL) and 2M potassium carbonate (21.72 mL, 43.4 mmol). The reaction was capped and flushed with N2 then PdCl2(dppf)-CH2Cl2 adduct (0.591 g, 0.724 mmol) was added. The reaction was then refluxed overnight under an inert atmosphere. The reaction mixture was cooled to room temperature and then filtered through a silica plug. Then diluted with 150 mL H2O and extracted with ethyl acetate (3×150 mL). The organics were combined and dried over Na2SO4 and then concentrated to a black residue. This was then purified via normal phase chromatography (50-100% EtOAc/Hexanes). Product fractions were combined and concentrated to afford 1,1-dimethylethyl 5-(4-aminothieno[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate (5.19 g, 13.42 mmol, 93% yield) as an off white solid. LC/MS (ES) m/z=368.2 [M+H]+

Workup

  1. customThe reaction was capped
  2. customflushed with N2
  3. temperatureThe reaction was then refluxed overnight under an inert atmosphere
  4. filtrationfiltered through a silica plug
  5. additionThen diluted with 150 mL H2O
  6. extractionextracted with ethyl acetate (3×150 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to a black residue
  9. customThis was then purified via normal phase chromatography (50-100% EtOAc/Hexanes)
  10. concentrationconcentrated

Sources & evidence

ORD record
ord-e722a2495c1244ea9568d05daabefd62
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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