((4-(1-ethylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acid → 5-(2-(3-(2-(4-Hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid ethylamide

HRID 2376858Notes

Reaction equation

HRID 2376858 reaction equation
[CH2:1]([NH:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]([NH:25][CH2:26][C:27](O)=[O:28])=[O:24])[CH:17]=3)=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)=[O:5])[CH3:2].Cl.[OH:31][C:32]1([CH3:38])[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>>[CH2:1]([NH:3][C:4]([N:6]1[C:14]2[C:9](=[CH:10][C:11]([O:15][C:16]3[CH:21]=[CH:20][N:19]=[C:18]([NH:22][C:23]([NH:25][CH2:26][C:27]([N:35]4[CH2:36][CH2:37][C:32]([OH:31])([CH3:38])[CH2:33][CH2:34]4)=[O:28])=[O:24])[CH:17]=3)=[CH:12][CH:13]=2)[CH:8]=[CH:7]1)=[O:5])[CH3:2]

Participants

3

Reactant 2

HCID 21949268((4-(1-ethylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acidHCID 219492954-Methylpiperidin-4-ol hydrochloride

Product 1

HCID 103910235-(2-(3-(2-(4-Hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid ethylamideYield 22%

Procedure

The reaction similar to Example 5 was performed by using ((4-(1-ethylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acid (149 mg, 0.37 mmol) and 4-hydroxy-4-methylpiperidine monohydrochloride (68 mg, 0.45 mmol, Production example 8-3); purification was performed by silica gel column chromatography (Fuji Silysia BW-300, eluent, ethyl acetate:methanol=9:1; Fuji Silysia NH, eluent, ethyl acetate:methanol=10:1; and again Fuji Silysia BW-300, eluent, ethyl acetate-methanol system); and the obtained crystals were suspended in diethyl ether and filtered off, washed with diethyl ether and dried under aeration to yield the title compound as colorless crystals (40 mg, 0.081 mmol, 22%).

Workup

  1. customThe reaction similar to Example 5
  2. custompurification
  3. filtrationfiltered off
  4. washwashed with diethyl ether
  5. customdried under aeration

Sources & evidence

ORD record
ord-1c57ba7801214f32841672016350c585
Source dataset
uspto-grants-2008_12
Patent number
US07468380B2

Reaction notes

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