Sodium Bicarbonate → HCID 86663679, compound

HRID 1909951Notes

Reaction equation

HRID 1909951 reaction equation
I[C:2]1[C:3]2[S:11][CH:10]=[C:9]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]([C:21](=[O:29])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:16][CH2:15]4)[C:4]=2[C:5]([NH2:8])=[N:6][CH:7]=1.[CH:30]([C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1)=[O:31].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>[NH2:8][C:5]1[C:4]2[C:9]([C:12]3[CH:13]=[C:14]4[C:18](=[CH:19][CH:20]=3)[N:17]([C:21](=[O:29])[CH2:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[CH2:16][CH2:15]4)=[CH:10][S:11][C:3]=2[C:2]([C:36]2[CH:37]=[C:32]([CH:33]=[CH:34][CH:35]=2)[CH:30]=[O:31])=[CH:7][N:6]=1

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 27343563-Formylphenylboronic acidHCID 66561009HCID 66561009, compound

Product 1

HCID 86663679HCID 86663679, compoundYield 68.9%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 7-iodo-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-4-amine (100 mg, 0.196 mmol), 3-formylphenyl boronic acid (40 mg, 0.267 mmol), and PdCl2(dppf)-CH2Cl2 adduct (9 mg, 0.011 mmol) in 1,4-Dioxane (1.5 mL) and saturated aqueous sodium bicarbonate (0.6 mL, 0.600 mmol) was degassed with Nitrogen for 10 minutes in a microwave vial. The vial was then capped and the mixture was stirred at 120° C. in the microwave for 30 min. LCMS showed complete and relatively clean conversion to the desired product. The mixture was cooled, poured into water (15 mL), and extracted with ethyl acetate (2×15 mL). The extracts were washed with brine (1×15 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 24 g SiO2, 20%-100% EtOAc in hexanes gradient over 35 minutes) to give 3-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}benzaldehyde (66 mg, 0.135 mmol, 68.9% yield) as a tan solid. LC/MS (ES) m/z=490 [M+H]+.

Workup

  1. customwas degassed with Nitrogen for 10 minutes in a microwave vial
  2. customThe vial was then capped
  3. temperatureThe mixture was cooled
  4. additionpoured into water (15 mL)
  5. extractionextracted with ethyl acetate (2×15 mL)
  6. washThe extracts were washed with brine (1×15 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (Analogix, 24 g SiO2, 20%-100% EtOAc in hexanes gradient over 35 minutes)

Sources & evidence

ORD record
ord-a2f2c491469846aa98252303cd231291
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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