Chlorine → Tws119

HRID 851910

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HRID 851910 반응식
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

참가 물질

6

반응물 4

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

생성물 1

HCID 9549289Tws119수율 50%

시약·촉매·용매 1

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

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온도
80 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-c2e9f977602e4c1d965eb66186e66800
출처 데이터셋
uspto-grants-2007_08
특허 번호
US07253166B2

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