Water → 5-(2-(3-(2-(4-Hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamide

HRID 2215503Notes

Reaction equation

HRID 2215503 reaction equation
Cl.[OH:2][C:3]1([CH3:9])[CH2:8][CH2:7][NH:6][CH2:5][CH2:4]1.C(N(CC)CC)C.[CH3:17][NH:18][C:19]([N:21]1[C:29]2[C:24](=[CH:25][C:26]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]([NH:40][CH2:41][C:42](O)=[O:43])=[O:39])[CH:32]=3)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1)=[O:20].O>CN(C)C=O.C(OCC)(=O)C.O1CCCC1>[CH3:17][NH:18][C:19]([N:21]1[C:29]2[C:24](=[CH:25][C:26]([O:30][C:31]3[CH:36]=[CH:35][N:34]=[C:33]([NH:37][C:38]([NH:40][CH2:41][C:42]([N:6]4[CH2:7][CH2:8][C:3]([OH:2])([CH3:9])[CH2:4][CH2:5]4)=[O:43])=[O:39])[CH:32]=3)=[CH:27][CH:28]=2)[CH:23]=[CH:22]1)=[O:20]

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 21949209((4-(1-methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acidHCID 219492954-Methylpiperidin-4-ol hydrochloride

Product 1

HCID 104802985-(2-(3-(2-(4-Hydroxy-4-methylpiperidin-1-yl)-2-oxoethyl)ureido)pyridin-4-yloxy)-1H-indole-1-carboxylic acid methylamideYield 75.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21939870Tetrahydrofuran ethyl acetateSolvent

Procedure

4-Hydoxy-4-methylpiperidine hydrochloride (113 mg, 0.745 mmol) was suspended in N,N-dimethylformamide (3 ml), then triethylamine (1 ml) was added; benzotriazole-1-isooxytris(dimethylamino)phosphonium hexafluorophosphate (201 mg, 0.454 mmol) and ((4-(1-methylcarbamoyl-1H-indol-5-yloxy)pyridin-2-yl)aminocarbonylamino)acetic acid (145 mg, 0.378 mmol) were added thereto; and the reaction mixture was stirred at room temperature for 2 hours. After water was added to the reaction mixture, extraction was performed with ethyl acetate-tetrahydrofuran. The organic layer was washed with brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel; ethyl acetate, ethyl acetate:methanol=20:1, 10:1 in this order). After concentration under reduced pressure, the product was solidified with diethyl ether, suspended, filtered off, washed with diethyl ether, and dried under aeration to yield the title compound (137 mg, 0.285 mmol, 75.4%) as a colorless amorphous solid.

Workup

  1. washThe organic layer was washed with brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (Fuji Silysia NH silica gel
  5. concentrationAfter concentration under reduced pressure
  6. filtrationfiltered off
  7. washwashed with diethyl ether
  8. customdried under aeration

Sources & evidence

ORD record
ord-b69e2511be7e4698b3b542ec288cabf7
Source dataset
uspto-grants-2006_09
Patent number
US07109219B2

Reaction notes

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