Sodium Bicarbonate → 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate

HRID 1909972Notes

Reaction equation

HRID 1909972 reaction equation
Br[C:2]1[C:6]2[C:7]([NH2:11])=[N:8][CH:9]=[CH:10][C:5]=2[O: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-].[Na+]>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>[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][O:4][C:5]=2[CH:10]=[CH:9][N:8]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 184507953-Bromofuro[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 668240741,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylateYield 79.4%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-bromofuro[3,2-c]pyridin-4-amine (3.002 g, 14.09 mmol), 1,1-dimethylethyl 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (5.346 g, 15.48 mmol), and PdCl2(dppf)-CH2Cl2 adduct (0.573 g, 0.702 mmol) in 1,4-Dioxane (120 mL) and saturated aqueous sodium bicarbonate (43 mL, 43.0 mmol) was degassed with Nitrogen for 20 minutes. The mixture was then stirred at reflux under Nitrogen for 16 hours. It was then cooled, poured into half-saturated aqueous NaHCO3 (250 mL), and extracted with ethyl acetate (2×250 mL). The extracts were washed with brine (1×250 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 400 g SiO2, 20%-100% EtOAc in hexanes gradient over 60 minutes, then 100% EtOAc for 15 more minutes) to give 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-2,3-dihydro-1H-indole-1-carboxylate (3.93 g) as an off-white solid. LC/MS (ES) m/z=352 [M+H]+.

Workup

  1. customwas degassed with Nitrogen for 20 minutes
  2. temperatureat reflux under Nitrogen for 16 hours
  3. temperatureIt was then cooled
  4. additionpoured into half-saturated aqueous NaHCO3 (250 mL)
  5. extractionextracted with ethyl acetate (2×250 mL)
  6. washThe extracts were washed with brine (1×250 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (Analogix, 400 g SiO2, 20%-100% EtOAc in hexanes

Sources & evidence

ORD record
ord-32d2c6f68c684daa9f90f39882f295af
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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