Water → 4-[5-(2-Fluoro-4-aminocarbonyl-phenyl)-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

HRID 1471779Notes

Reaction equation

HRID 1471779 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]#[C:15][C:16]2[C:21](Cl)=[CH:20][N:19]=[C:18]([C:23]3[CH:28]=[CH:27][C:26]([C:29]#[N:30])=[CH:25][C:24]=3[F:31])[CH:17]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[OH-:32].[K+].C(P(C(C)(C)C)C1(C(C)C)CC(C(C)C)=CC(C(C)C)=C1C1C=CC=CC=1)(C)(C)C.[OH2:64]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C(Cl)(Cl)Cl.[Pd].[Pd].O1CCOCC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]2[O:64][C:21]3=[CH:20][N:19]=[C:18]([C:23]4[CH:28]=[CH:27][C:26]([C:29]([NH2:30])=[O:32])=[CH:25][C:24]=4[F:31])[CH:17]=[C:16]3[CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962Water2×HCID 14797Potassium HydroxideHCID 668498352-DI-Tert-Butylphosphino-2,4,6-TriisopropylbiphenylHCID 866945734-[5-Chloro-2-(4-cyano-2-fluoro-phenyl)-pyridin-4-ylethynyl]-piperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 717364174-[5-(2-Fluoro-4-aminocarbonyl-phenyl)-furo[2,3-c]pyridin-2-yl]-piperidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 11029508Palladium, tris[mu-[(1,2-eta:4,5-eta)-(1E,4E)-1,5-diphenyl-1,4-pentadien-3-one]]di-, compd. with trichloromethane (1:1)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A flask is charged under Ar atmosphere with a stir bar, 4-[5-chloro-2-(4-cyano-2-fluoro-phenyl)-pyridin-4-ylethynyl]-piperidine-1-carboxylic acid tert-butyl ester (110 mg), powdered KOH (42 mg), 2-di-tert-butylphosphino-2,4,6-triisopropylbiphenyl (8 mg), tris(dibenzylideneacetone)dipalladium(0) chloroform adduct (6 mg), water (1.5 mL), and 1,4-dioxane (3 mL). The mixture is heated to 110° C. and stirred at this temperature for 2 h. After cooling the mixture to room temperature, water is added and the resulting mixture is extracted with ethyl acetate. The combined extracts are washed with brine, dried (Na2SO4), and concentrated. The residue is chromatographed on silica gel [dichloromethane/(dichloromethane/methanol/7 M ammonia in methanol 50:48:2) 9:1] to give the title compound. LC (method 3): tR=1.26 min; Mass spectrum (ESI+): m/z=440 [M+H]+.

Workup

  1. additionA flask is charged under Ar atmosphere with a stir bar
  2. temperatureAfter cooling the mixture to room temperature
  3. extractionthe resulting mixture is extracted with ethyl acetate
  4. washThe combined extracts are washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated
  7. customThe residue is chromatographed on silica gel [dichloromethane/(dichloromethane/methanol/7 M ammonia in methanol 50:48:2) 9:1]

Sources & evidence

ORD record
ord-111f8376e6174daf84391cd7100ff4c5
Source dataset
uspto-grants-2015_04
Patent number
US09012456B2

Reaction notes

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