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

HRID 1471779노트

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HRID 1471779 반응식
[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]

참가 물질

7

반응물 4

HCID 962Water2회HCID 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

생성물 1

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

시약·촉매·용매 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)촉매HCID 312751,4-Dioxane용매

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온도
110 °C

실험 절차

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]+.

후처리

  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]

출처 및 근거

ORD 기록
ord-111f8376e6174daf84391cd7100ff4c5
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012456B2

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