Phosphate → 5-[5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]-7-carbamoylindolin-1-yl]-5-oxopentanoic acid

HRID 273859Notes

Reaction equation

HRID 273859 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH2:34][CH3:35])[CH:9]([CH3:23])[CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[C:18]([C:20]([NH2:22])=[O:21])[CH:19]=1)[NH:16][CH2:15][CH2:14]2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:36]1(=[O:43])[O:42][C:40](=[O:41])[CH2:39][CH2:38][CH2:37]1.P([O-])([O-])([O-])=O>N1C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([N:8]([CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=1[O:33][CH2:34][CH3:35])[CH:9]([CH3:23])[CH2:10][C:11]1[CH:12]=[C:13]2[C:17](=[C:18]([C:20](=[O:21])[NH2:22])[CH:19]=1)[N:16]([C:36](=[O:43])[CH2:37][CH2:38][CH2:39][C:40]([OH:42])=[O:41])[CH2:15][CH2:14]2)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 1061PhosphateHCID 7940Glutaric anhydrideHCID 200943485-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]indoline-7-carboxamide

Product 1

HCID 200943435-[5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]-7-carbamoylindolin-1-yl]-5-oxopentanoic acidYield 85.9%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 1049PyridineSolvent

Procedure

To a solution of 5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]indoline-7-carboxamide (145 mg) in pyridine (0.5 ml) were added 4-dimethylaminopyridine (4 mg) and glutaric anhydride (51 mg), and the mixture was stirred at room temperature for 72 hours. The pH of the reaction mixture was adjusted to pH 7 with phosphate buffer solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by medium pressure liquid column chromatography on silica gel using a mixture of chloroform and methanol (9/1) as eluent to give 154 mg of 5-[5-[2-[N-tert-butoxycarbonyl-2-(2-ethoxyphenoxy)ethylamino]propyl]-7-carbamoylindolin- 1-yl]-5-oxopentanoic acid as an oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by medium pressure liquid column chromatography on silica gel using
  6. additiona mixture of chloroform and methanol (9/1) as eluent

Sources & evidence

ORD record
ord-439f562608704768943b474f471d9b53
Source dataset
uspto-grants-1995_02
Patent number
US05387603

Reaction notes

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