Water → methyl 4-(4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl)thiophene-2-carboxylate

HRID 2206015Notes

Reaction equation

HRID 2206015 reaction equation
FC(F)(F)S(O[C:7]1[C:11]2[C:12]([O:16][CH3:17])=[N:13][CH:14]=[CH:15][C:10]=2[N:9]([CH:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)[N:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:34]2[CH:35]=[C:36]([C:39]([O:41][CH3:42])=[O:40])[S:37][CH:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:17][O:16][C:12]1[C:11]2[C:7]([C:34]3[CH:35]=[C:36]([C:39]([O:41][CH3:42])=[O:40])[S:37][CH:38]=3)=[N:8][N:9]([CH:18]3[CH2:19][CH2:20][O:21][CH2:22][CH2:23]3)[C:10]=2[CH:15]=[CH:14][N:13]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 52911233Methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylateHCID 1179885614-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate

Product 1

HCID 117987879methyl 4-(4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl)thiophene-2-carboxylateYield 68.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

A solution of 4-methoxy-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate (250 mg) obtained in Step A of Example 15, methyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)thiophene-2-carboxylate (264 mg), tetrakis(triphenylphosphine)palladium(0) (76.0 mg) and 2M aqueous sodium carbonate solution (1.60 mL) in DME (15 mL) was heated overnight with reflux under nitrogen atmosphere. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (167 mg).

Workup

  1. temperaturewith reflux under nitrogen atmosphere
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe organic layer was washed successively with water and saturated brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-0fdd70879f734c0aaffd3d5e89c84b6a
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

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