Methanol → HCID 53467819, compound

HRID 1909927Notes

Reaction equation

HRID 1909927 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.[N:30]1[CH:35]=[CH:34][C:33](B(O)O)=[CH:32][CH:31]=1.C(=O)(O)[O-].[Na+].CO>O1CCOCC1.CCOC(C)=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].C(Cl)Cl>[C:23]1([CH2:22][C:21]([N:17]2[C:18]3[C:14](=[CH:13][C:12]([C:9]4[C:4]5[C:5]([NH2:8])=[N:6][CH:7]=[C:2]([C:33]6[CH:34]=[CH:35][N:30]=[CH:31][CH:32]=6)[C:3]=5[S:11][CH:10]=4)=[CH:20][CH:19]=3)[CH2:15][CH2:16]2)=[O:29])[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 66561009HCID 66561009, compound

Product 1

HCID 53467819HCID 53467819, compoundYield 68.6%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 8857Ethyl AcetateSolventHCID 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 (101 mg, 0.198 mmol), pyridine-4-boronic acid, pinacol ester (53 mg, 0.258 mmol), and PdCl2(dppf)-CH2Cl2 adduct (8 mg, 9.80 μmol) 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 conversion to the desired product, along with a small de-iodo by-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, 25%-100% EtOAc in hexanes gradient over 30 minutes, then EtOAc for 10 minutes, then 0-10% MeOH in EtOAc over 20 minutes) to give 3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]-7-(4-pyridinyl)thieno[3,2-c]pyridin-4-amine (66 mg, 0.136 mmol, 68.6% yield) as a beige solid. LC/MS (ES) m/z=463 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.24 (t, J=8.46 Hz, 2H), 3.90 (s, 2H), 4.26 (t, J=8.46 Hz, 2H), 5.74 (br. s., 2H), 7.23-7.39 (m, 7H), 7.52 (s, 1H), 7.70-7.75 (m, 2H), 8.09 (s, 1H), 8.18 (d, J=8.34 Hz, 0H), 8.65-8.72 (m, 2H).

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, 25%-100% EtOAc in hexanes
  11. waitgradient over 30 minutes
  12. waitEtOAc for 10 minutes

Sources & evidence

ORD record
ord-be3ad7d114664b8d9cee364378d1f245
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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