Potassium Fluoride → 7-(1,2-dihydroxyethyl)-3-(1-methyl-1H-pyrazol-4-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

HRID 1987128ノート

反応式

HRID 1987128 の反応式
Cl[C:2]1[CH:3]=[C:4]2[C:12](=[O:13])[C:11]3[CH:14]=[C:15]([CH:18]([OH:21])[CH2:19][OH:20])[CH:16]=[CH:17][C:10]=3[CH:9]=[CH:8][C:5]2=[N:6][CH:7]=1.[CH3:22][N:23]1[CH:27]=[C:26](B2OC(C)(C)C(C)(C)O2)[CH:25]=[N:24]1.[F-].[K+]>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.[Pd].[Pd]>[OH:21][CH:18]([C:15]1[CH:16]=[CH:17][C:10]2[CH:9]=[CH:8][C:5]3=[N:6][CH:7]=[C:2]([C:26]4[CH:25]=[N:24][N:23]([CH3:22])[CH:27]=4)[CH:3]=[C:4]3[C:12](=[O:13])[C:11]=2[CH:14]=1)[CH2:19][OH:20]

参加物

5

反応物 3

HCID 522689Potassium FluorideHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 577228643-chloro-7-(1,2-dihydroxyethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

生成物 1

HCID 160358507-(1,2-dihydroxyethyl)-3-(1-methyl-1H-pyrazol-4-yl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one

試薬・触媒・溶媒 1

HCID 9811564Bis(dibenzylideneacetone)palladium触媒

反応条件

温度
180 °C

実験手順

A test tube fitted with a teflon septum was charged with 3-chloro-7-(1,2-dihydroxyethyl)-5H-benzo[4,5]cyclohepta[1,2-b]pyridin-5-one (9 mg, 0.03 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (12 mg, 0.060 mmol), Pd2(dba)3 (1 mg, 0.001 mmol), (tBu3)PBF4 (1 mg, 0.003 mmol) and potassium fluoride (6 mg, 0.098 mmol). The tube was evacuated and backfilled with argon three times. Fully degassed DMF (0.9 mL) was added and the reaction was heated in a microwave at 180° C. for 30 min. The reaction was poured into an ethyl acetate/brine mixture and washed twice with brine. The organic layer was dried over magnesium sulfate, filtered, concentrated in vacuo, and purified via reverse phase HPLC (10-70% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier) to afford the title compound. 1H NMR (600 MHz, CDCl3) δ 9.00 (d, 1H); 8.58 (d, 1H); 8.27 (s, 1H); 7.91 (s, 1H); 7.81 (s, 1H); 7.75 (d, 1H); 7.61 (d, 1H); 7.38 (d, 1H); 7.24 (d, 1H); 5.0 (dd, 1H); 3.99 (s, 3H); 3.87 (dd, 1H); 3.72 (d, 1H). Hydroxyl/protons were not observed. LRMS (APCI) calc'd for (C20H18N3O3) [M+H]+, 348.1; found 348.1.

後処理

  1. customThe tube was evacuated
  2. additionFully degassed DMF (0.9 mL) was added
  3. additionThe reaction was poured into an ethyl acetate/brine mixture
  4. washwashed twice with brine
  5. dry with materialThe organic layer was dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. custompurified via reverse phase HPLC (10-70% acetonitrile/water gradient, 0.05% trifluoroacetic acid modifier)

出典と根拠

ORDレコード
ord-16a8fd2510b4464ab1e815d89ef892e5
出典データセット
uspto-grants-2009_06
特許番号
US07550478B2

反応ノート

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