Water → ethyl 5-({[4-(cyclopropylmethoxy)phenyl]carbonyl}amino)-1,4-dimethyl-1H-indole-2-carboxylate

HRID 239904Notes

Reaction equation

HRID 239904 reaction equation
[CH2:1]([N:3]([CH:7]([CH3:9])[CH3:8])[CH:4]([CH3:6])[CH3:5])C.[CH:10]1([CH2:13][O:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=2)[CH2:12][CH2:11]1.[OH2:24].O[N:26]1[C:30]2[CH:31]=CC=[CH:34][C:29]=2N=N1.Cl.C(N=C=NC[CH2:42][CH2:43]N(C)C)C.[OH2:47]>CN(C=O)C.C(OCC)(=O)C.C1COCC1>[CH:10]1([CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([C:19]([NH:26][C:30]3[C:29]([CH3:34])=[C:8]4[C:7](=[CH:9][CH:31]=3)[N:3]([CH3:1])[C:4]([C:6]([O:47][CH2:42][CH3:43])=[O:24])=[CH:5]4)=[O:21])=[CH:22][CH:23]=2)[CH2:11][CH2:12]1

Participants

9

Reactant 5

HCID 962WaterHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 226453014-(Cyclopropylmethoxy)benzoic acid

Product 1

HCID 70968097ethyl 5-({[4-(cyclopropylmethoxy)phenyl]carbonyl}amino)-1,4-dimethyl-1H-indole-2-carboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 5-amino-1,4-dimethyl-1H-indole-2-carboxylate hydrochloride (400 mg) obtained in Reference Example 45 was suspended in DMF (4.0 mL), ethyldiisopropylamine (0.25 mL), 4-(cyclopropylmethoxy)benzoic acid (300 mg), 1-hydroxybenzotriazole monohydrate (456 mg), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (568 mg) and N,N-dimethylaminopyridine (200 mg) were successively added, and the mixture was stirred at room temperature for 22 hr. After dilution with THF and ethyl acetate, water was added. The organic layer was washed twice with water, and concentrated under reduced pressure. The residue was suspended in diisopropyl ether, and the precipitate was collected by filtration, washed with diisopropyl ether, and dried under reduced pressure to give the title compound (547 mg, yield 90%) as a white solid.

Workup

  1. washThe organic layer was washed twice with water
  2. concentrationconcentrated under reduced pressure
  3. filtrationthe precipitate was collected by filtration
  4. washwashed with diisopropyl ether
  5. customdried under reduced pressure

Sources & evidence

ORD record
ord-80be2a56bb784e7685f13293bb191226
Source dataset
uspto-grants-2014_02
Patent number
US08642770B2

Reaction notes

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