((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 2215534Notes

Reaction equation

HRID 2215534 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-5a3395b39a084a79a5d8b166ec877c34
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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