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

HRID 1910087Notes

Reaction equation

HRID 1910087 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.[F:12][C:13]1[C:21](B2OC(C)(C)C(C)(C)O2)=[CH:20][CH:19]=[C:18]2[C:14]=1[CH2:15][CH2:16][N:17]2[C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32].C(=O)(O)[O-].[Na+]>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:21]3[C:13]([F:12])=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]([C:31]([O:33][C:34]([CH3:36])([CH3:35])[CH3:37])=[O:32])[CH2:16][CH2:15]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 66823308Tert-butyl 4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)indoline-1-carboxylate

Product 1

HCID 668239041,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylateYield 38.1%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-Bromofuro[3,2-c]pyridin-4-amine (310 mg, 1.455 mmol), 1,1-dimethylethyl 4-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole-1-carboxylate (577 mg, 1.589 mmol), PdCl2(dppf)-CH2Cl2 adduct (65 mg, 0.080 mmol), 1,4-Dioxane (15 mL), and saturated aqueous sodium bicarbonate (4.5 mL, 4.50 mmol) were added to a 200 mL flask equipped with a reflux condenser. The flask was evacuated and filled with nitrogen 4 times, and then the mixture was stirred at 100° C. under Nitrogen for 15 hours. LCMS showed complete and clean conversion, so it was cooled and filtered through celite, rinsing with EtOAc (50 mL). The filtrate was washed with half-saturated aqueous NaHCO3 (50 mL), and the aqueous phase was back-extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (1×100 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 60 g SiO2, 10%-75% EtOAc in hexanes gradient over 60 minutes) to give 1,1-dimethylethyl 5-(4-aminofuro[3,2-c]pyridin-3-yl)-4-fluoro-2,3-dihydro-1H-indole-1-carboxylate (205 mg, 0.555 mmol, 38.1% yield) as an off-white solid. LC/MS (ES) m/z=370 [M+H]+

Workup

  1. customequipped with a reflux condenser
  2. customThe flask was evacuated
  3. additionfilled with nitrogen 4 times
  4. temperatureclean conversion, so it was cooled
  5. filtrationfiltered through celite
  6. washrinsing with EtOAc (50 mL)
  7. washThe filtrate was washed with half-saturated aqueous NaHCO3 (50 mL)
  8. extractionthe aqueous phase was back-extracted with ethyl acetate (2×50 mL)
  9. washThe combined organic phases were washed with brine (1×100 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe residue was purified by flash chromatography (Analogix, 60 g SiO2, 10%-75% EtOAc in hexanes gradient over 60 minutes)

Sources & evidence

ORD record
ord-cb8b46981f3e4db59e954d5faf66ab15
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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