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

HRID 31117

Reaction equation

HRID 31117 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)[NH:5][C:4]1=[O:13].[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]([C:24](O)=[O:25])=[CH:18]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>[Cl:14][C:15]1[CH:16]=[C:17]2[C:21](=[CH:22][CH:23]=1)[NH:20][C:19]([C:24]([NH:2][C@@H:3]1[CH2:12][C:11]3[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=3)[NH:5][C:4]1=[O:13])=[O:25])=[CH:18]2

Participants

8

Reactant 5

HCID 81531DiisopropylethylamineHCID 826935-Chloro-1H-indole-2-carboxylic acidHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57462920(R)-3-Amino-3,4-dihydroquinolin-2(1H)-one hydrochloride

Product 1

HCID 9840862(R)-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyrilYield 81.2%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Alternatively, (R)-3-amino-3,4-dihydrocarbostyril hydrochloride (95 mg) was added to a mixture of tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (103 mg), 1-hydroxy-7-azabenzotriazole (85 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (120 mg) at room temperature. Diisopropylethylamine (186 mg) was added, and the resulting yellow suspension was stirred for 2 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), 1.0 M aqueous sodium hydroxide (25 mL), and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated under vacuum. The resulting solid crude product was triturated with diethyl ether (5 mL twice), then 50% methanol in diethyl ether (5 mL twice). Drying under vacuum provided pure title compound (132 mg).

Workup

  1. customformed
  2. washwashed sequentially with 1.0 M aqueous hydrochloric acid (25 mL), 1.0 M aqueous sodium hydroxide (25 mL), and brine (25 mL)
  3. dry with materialdried over anhydrous sodium sulfate
  4. customevaporated under vacuum
  5. customThe resulting solid crude product was triturated with diethyl ether (5 mL twice), then 50% methanol in diethyl ether (5 mL twice)
  6. customDrying under vacuum

Sources & evidence

ORD record
ord-0bf3dd07fac242baa15f35579ffa3812
Source dataset
uspto-grants-2008_09
Patent number
US07425550B2

Linked notes

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