Chlorine → Tws119

HRID 851910

Reaction equation

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

Participants

Conditions

Temperature: 80 °C

Procedure

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).

Workup

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

Sources & evidence

ORD record: ord-c2e9f977602e4c1d965eb66186e66800
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07253166B2

Linked notes

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