Ethyl Acetate → HCID 66823627, compound

HRID 1909939Notes

Reaction equation

HRID 1909939 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.B1([C:39]2[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH:40]=2)OC(C)(C)C(C)(C)O1.C(=O)(O)[O-].[Na+].CCOC(C)=O>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:39]2[CH2:44][CH2:43][N:42]([C:45]([O:47][C:48]([CH3:51])([CH3:50])[CH3:49])=[O:46])[CH2:41][CH:40]=2)=[CH:7][N:6]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 516892Sodium BicarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 66561009HCID 66561009, compound

Product 1

HCID 66823627HCID 66823627, compoundYield 85%

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 (298 mg, 0.583 mmol), 3,6-dihydro-2H-pyridine-1-N-Boc-4-boronic acid pinacol ester (238 mg, 0.770 mmol), and PdCl2(dppf)-CH2Cl2 adduct (24 mg, 0.029 mmol) in 1,4-Dioxane (6 mL) and saturated aqueous sodium bicarbonate (2 mL, 2.000 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 reactor for 30 min. LCMS showed complete conversion to the product. The mixture was cooled, poured into water (50 mL), and extracted with ethyl acetate (2×50 mL). The extracts were washed with brine (1×75 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography (Analogix, 40 g SiO2, 25%-100% EtOAc in hexanes gradient over 45 minutes, then EtOAc for 5 minutes) to give 1,1-dimethylethyl 4-{4-amino-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-7-yl}-3,6-dihydro-1(2H)-pyridinecarboxylate (280 mg, 0.494 mmol, 85% yield) as a beige solid. LC/MS (ES) m/z=567 [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 (50 mL)
  5. extractionextracted with ethyl acetate (2×50 mL)
  6. washThe extracts were washed with brine (1×75 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash chromatography (Analogix, 40 g SiO2, 25%-100% EtOAc in hexanes
  11. waitgradient over 45 minutes

Sources & evidence

ORD record
ord-0e4dcc37d82a479ca91b1144b3038229
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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