Hydrochloric Acid → 6-Fluoro-5-[4-(tetrahydro-2H-pyran-4-yl)phenyl]-1H-indazole-3-carboxylic acid

HRID 1054839ノート

反応式

HRID 1054839 の反応式
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[NH:7][N:6]=[C:5]2[C:12]([OH:14])=[O:13].CC1(C)COB([C:22]2[CH:27]=[CH:26][C:25]([CH:28]3[CH2:33][CH2:32][O:31][CH2:30][CH2:29]3)=[CH:24][CH:23]=2)OC1.C(=O)([O-])[O-].[K+].[K+].Cl>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].C1(C)C=CC=CC=1.C(O)C>[F:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([C:12]([OH:14])=[O:13])=[N:6][NH:7]2)=[CH:3][C:2]=1[C:22]1[CH:23]=[CH:24][C:25]([CH:28]2[CH2:29][CH2:30][O:31][CH2:32][CH2:33]2)=[CH:26][CH:27]=1

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 866988305,5-Dimethyl-2-(4-(tetrahydro-2H-pyran-4-yl)phenyl)-1,3,2-dioxaborinaneHCID 866988325-bromo-6-fluoro-1H-indazole-3-carboxylic acid

生成物 1

HCID 866988316-Fluoro-5-[4-(tetrahydro-2H-pyran-4-yl)phenyl]-1H-indazole-3-carboxylic acid収率 11%

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 702Ethanol溶媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

A mixture of 5-bromo-6-fluoro-1H-indazole-3-carboxylic acid (793 mg, 3.06 mmol), 5,5-dimethyl-2-[4-(tetrahydro-2H-pyran-4-yl)phenyl]-1,3,2-dioxaborinane (839 mg, 3.06 mmol) and [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (175 mg, 0.214 mmol) were sealed in a vial and purged with nitrogen. Ethanol (4 mL), toluene (2 mL) and aqueous 2 M potassium carbonate (3.67 ml, 7.34 mmol) were added and the mixture was heated at 110° C. for 50 minutes. The cooled reaction mixture was poured into dilute HCl and extracted with ethyl acetate. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo to give crude material, which was purified using reverse-phase chromatography. The product was crystallized from isopropanol/hexane to give the title compound as a crystalline solid (110 mg, 11% yield). MS (ES−) 339.1 (M−H)−. 1H NMR (500 MHz, CD3OD) δ 8.34 (d, J=7.32 Hz, 1 H), 7.54 (d, 2H), 7.35 (d, 2H), 7.27 (d, J=10.25 Hz, 1H), 4.08 (d, J=10.25 Hz, 2H), 3.61 (td, J=10.98, 3.42 Hz, 2H), 2.88 (m, 1H), 1.81-1.90 (m, 4H). m.p.=295° C.

後処理

  1. customwere sealed in a vial and
  2. custompurged with nitrogen
  3. customThe cooled reaction mixture
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give crude material, which
  9. customwas purified
  10. customThe product was crystallized from isopropanol/hexane

出典と根拠

ORDレコード
ord-c0f4e1af6c0f4a08a44d8ac327dd62c3
出典データセット
uspto-grants-2016_07
特許番号
US09394285B2

反応ノート

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