Chlorine → Tws119

HRID 851910

反応式

HRID 851910 の反応式
Br[C:2]1[NH:18][C:5]2[N:6]=[CH:7][N:8]=[C:9]([O:10][C:11]3[CH:12]=[CH:13][CH:14]=[C:15]([OH:17])[CH:16]=3)[C:4]=2[CH:3]=1.ClCl.[O-]P([O-])([O-])=O.[K+].[K+].[K+].O1[CH2:34][CH2:33]OCC1>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]>[NH2:6][C:5]1[CH:4]=[C:3]([C:2]2[NH:18][C:5]3[N:6]=[CH:7][N:8]=[C:9]([O:10][C:11]4[CH:16]=[C:15]([OH:17])[CH:14]=[CH:13][CH:12]=4)[C:4]=3[CH:3]=2)[CH:2]=[CH:33][CH:34]=1

参加物

6

反応物 4

HCID 24526ChlorineHCID 312751,4-DioxaneHCID 62657Potassium Phosphate, TribasicHCID 694901713-[(6-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-yl)oxy]phenol

生成物 1

HCID 9549289Tws119収率 50%

試薬・触媒・溶媒 1

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

反応条件

温度
80 °C

実験手順

5-(6-bromo-7H-pyrrolo[2,3-d]pyrimidin-4-yloxyl)-phenol (14 mg, 0.0448 mmol) is mixed with 3-amninophenylboronic acid (13 mg, 0.0896 mmol), Pd(dppf)Cl2.CH2.Cl2 (7.5 mg, 0.009 mmol), and K3PO4 (19 mg, 0.0896 mmol) in anhydrous dioxane (0.8 mL) under an argon atmosphere. The mixture is heated to 80° C. for 18 hours, with stirring. The reaction is then cooled to ambient temperature and filtered through a pad of silica with 10% MeOH in DCM. The filtrate is concentrated and the resulting crude product is purified by reverse phase HPLC using a C18 column and 0-95% acetonitrile/water gradient to give 3-[6-(3-amino-phenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yloxy]-phenol (7.1 mg, 50%); 1H NMR (500 MHz, DMSO): δ 8.27 (s, 1H), 7.29 (t, J=8.1 Hz, 1H), 7.20 (t, J=7.9 Hz, 1H), 7.10-7.17 (m, 2H), 6.68-7.08 (m, 4H), 6.52 (s, 1H); LC-ESMS observed [M+H]+ 319.1 (calculated for C18H14N4O2, 318.11).

後処理

  1. temperatureThe reaction is then cooled to ambient temperature
  2. filtrationfiltered through a pad of silica with 10% MeOH in DCM
  3. concentrationThe filtrate is concentrated
  4. customthe resulting crude product is purified by reverse phase HPLC

出典と根拠

ORDレコード
ord-c2e9f977602e4c1d965eb66186e66800
出典データセット
uspto-grants-2007_08
特許番号
US07253166B2

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