Diisopropylethylamine → (R)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril

HRID 31121

Reaction equation

HRID 31121 reaction equation
Cl.[NH2:2][C@@H:3]1[CH2:12][C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[C:4]1=[O:18].[Cl:19][C:20]1[CH:21]=[C:22]2[C:26](=[CH:27][CH:28]=1)[NH:25][C:24]([C:29](O)=[O:30])=[CH:23]2.ON1C2N=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>C(OCC)(=O)C.O1CCCC1>[C:14]([CH2:13][N:5]1[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[CH2:12][C@@H:3]([NH:2][C:29]([C:24]2[NH:25][C:26]3[C:22]([CH:23]=2)=[CH:21][C:20]([Cl:19])=[CH:28][CH:27]=3)=[O:30])[C:4]1=[O:18])([O:16][CH3:17])=[O:15]

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 69197166(R)-3-amino-1-carbomethoxymethyl-3,4-dihydrocarbostyril hydrochloride

Product 1

HCID 69194658(R)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyrilYield 26.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Alternatively, (R)-3-amino-1-carbomethoxymethyl-3,4-dihydrocarbostyril hydrochloride (19 mg) was added to a mixture of tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (15 mg), 1-hydroxy-7-azabenzotriazole (12 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (16 mg) at room temperature. Diisopropylethylamine (19 mg) was added, and the resulting yellow suspension was stirred under argon for 16 h, during which a solution formed. The solution was diluted with ethyl acetate (50 mL) and washed sequentially with 1.0 M aqueous hydrochloric acid (25 mL twice), 1.0 M aqueous sodium hydroxide (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate and evaporated under vacuum. One half of the residue was purified by reverse phase preparative HPLC to provide the title compound (7.6 mg).

Workup

  1. customformed
  2. washwashed sequentially with 1.0 M aqueous hydrochloric acid (25 mL twice), 1.0 M aqueous sodium hydroxide (20 mL) and brine (20 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated under vacuum
  5. customOne half of the residue was purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-7b8dc316b972470cb45b94360bef18ca
Source dataset
uspto-grants-2008_09
Patent number
US07425550B2

Linked notes

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