Methanol → HCID 53466951, compound

HRID 1909932Notes

Reaction equation

HRID 1909932 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.[CH3:30][N:31]1[CH:35]=[C:34](B2OC(C)(C)C(C)(C)O2)[CH:33]=[N:32]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>[CH3:30][N:31]1[CH:35]=[C:34]([C:2]2[C:3]3[S:11][CH:10]=[C:9]([C:12]4[CH:13]=[C:14]5[C:18](=[CH:19][CH:20]=4)[N:17]([C:21](=[O:29])[CH2:22][C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH2:16][CH2:15]5)[C:4]=3[C:5]([NH2:8])=[N:6][CH:7]=2)[CH:33]=[N:32]1

Participants

8

Reactant 4

HCID 887MethanolHCID 516892Sodium BicarbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 66561009HCID 66561009, compound

Product 1

HCID 53466951HCID 53466951, compoundYield 70.9%

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 (102 mg, 0.199 mmol), 1-methylpyrazole-4-boronic acid pinacol ester (60 mg, 0.288 mmol), and PdCl2(dppf)-CH2Cl2 adduct (8 mg, 9.80 μmol) in 1,4-Dioxane (2.0 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. 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, 50%-100% EtOAc in hexanes gradient over 10 minutes, then EtOAc for 5 minutes, then 0-10% MeOH in EtOAc over 20 minutes) to give 7-(1-methyl-1H-pyrazol-4-yl)-3-[1-(phenylacetyl)-2,3-dihydro-1H-indol-5-yl]thieno[3,2-c]pyridin-4-amine (69 mg, 0.141 mmol, 70.6% yield) as a light gray solid. LC/MS (ES) m/z=466 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ 3.24 (t, J=8.46 Hz, 2H), 3.89 (s, 2H), 3.93 (s, 3H), 4.26 (t, J=8.46 Hz, 2H), 5.41 (br. s., 2H), 7.22-7.30 (m, 2H), 7.30-7.39 (m, 5H), 7.49 (s, 1H), 7.88 (s, 1H), 8.03 (s, 1H), 8.14 (s, 1H), 8.17 (d, J=8.08 Hz, 1H).

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, 50%-100% EtOAc in hexanes
  11. waitgradient over 10 minutes
  12. waitEtOAc for 5 minutes

Sources & evidence

ORD record
ord-23324c59fcad4756b58fc23858d670a6
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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