Water → methyl (5-{3-[[5-fluoro-2-(4-methoxyphenyl)-4-pyrimidinyl](methyl)amino]propoxy}-1H-indol-1-yl)acetate

HRID 2424989Notes

Reaction equation

[CH3:1][O:2][C:3](=[O:28])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH2:15][CH2:16][CH2:17][N:18]([C:20]3[C:25]([F:26])=[CH:24][N:23]=[C:22](Cl)[N:21]=3)[CH3:19])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1.O.C(=O)([O-])[O-].[Na+].[Na+].[CH3:36][O:37][C:38]1[CH:43]=[CH:42][C:41](B(O)O)=[CH:40][CH:39]=1>C1(C)C=CC=CC=1.O1CCOCC1>[CH3:1][O:2][C:3](=[O:28])[CH2:4][N:5]1[C:13]2[C:8](=[CH:9][C:10]([O:14][CH2:15][CH2:16][CH2:17][N:18]([C:20]3[C:25]([F:26])=[CH:24][N:23]=[C:22]([C:41]4[CH:42]=[CH:43][C:38]([O:37][CH3:36])=[CH:39][CH:40]=4)[N:21]=3)[CH3:19])=[CH:11][CH:12]=2)[CH:7]=[CH:6]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of methyl(5-{3-[(2-chloro-5-fluoro-4-pyrimidinyl)(methyl)amino]propoxy}-1H-indol-1-yl)acetate (Example 84, 0.1 g, 0.25 mmol) in toluene (3.75 mL), dioxane (0.75 mL), and water (0.88 mL) were added sodium carbonate (0.26 g, 2.46 mmol), 4-methoxyphenyl boronic acid (0.15 g, 0.98 mmol), and PdCl2(dppf)(CH2Cl2) (0.04 g, 0.05 mmol). The mixture was heated at 80° C. for 4 h and then concentrated under reduced pressure. The product (0.11 g, 94%) was obtained after column chromatography (67% hexanes in EtOAc). 1H NMR (300 MHz, CD2Cl2) δ 8.31 (d, 2H), 8.06 (d, 1H), 7.12-7.07 (m, 3H), 6.95-6.87 (m, 3H), 6.41 (d, 1H), 4.85 (s, 2H), 4.11 (t, 2H), 3.94 (t, 2H), 3.86 (s, 3H), 3.76 (s, 3H), 3.35 (d, 3H), 2.26-2.20 (m, 2H).

Workup

concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-331c4f779ecb42f989b3a3f786e8ba85
Source dataset: uspto-grants-2011_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07964622B2

Reaction notes

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