p-Toluidine → HCID 9893626, compound

HRID 378725Notes

Reaction equation

HRID 378725 reaction equation
[CH2:1]([O:3][CH:4]([O:31][CH2:32][CH3:33])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:26][C:27](O)=[O:28])([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([CH3:25])=[CH:21][CH:20]=2)=[O:17])[C:7]1=[O:30])[CH3:2].Cl.C(N=C=NCCCN(C)C)C.[NH2:46][C:47]1[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=1>ClCCl.CN(C)C1C=CN=CC=1>[CH2:32]([O:31][CH:4]([O:3][CH2:1][CH3:2])[CH2:5][N:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([CH2:26][C:27]([NH:46][C:47]2[CH:52]=[CH:51][C:50]([CH3:53])=[CH:49][CH:48]=2)=[O:28])([NH:15][C:16]([NH:18][C:19]2[CH:20]=[CH:21][C:22]([CH3:25])=[CH:23][CH:24]=2)=[O:17])[C:7]1=[O:30])[CH3:33]

Participants

6

Reactant 3

HCID 7813p-ToluidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 15458211HCID 15458211, compound

Product 1

HCID 9893626HCID 9893626, compoundYield 116.5%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

In 100 ml of dichloromethane was dissolved 2.8 g of (+)-1-(2,2-diethoxyethyl)-3-hydroxycarbonylmethyl-3-(N'-(4-methylphenyl)ureido)indolin-2-one, and 1.20 g of 4-dimethylaminopyridine, 1.90 g of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride, and 1.10 g of p-toluidine were successively added thereto. The mixture was stirred for 18 hours and concentrated. The concentrate was diluted with ethyl acetate, washed successively with dilute hydrochloric acid and saturated aqueous sodium hydrogencarbonate. The organic layer was dried over anhydrous sodium sulfate, and concentrated. The crude product was purified by silica gel column chromatography (hexane/ethyl acetate=2/1) to yield 3.90 g (81%) of the title compound as a white powder. The resulting compound was found to be optically pure as analyzed by high performance liquid chromatography using an optically active column (CHIRALCEL OD, produced by Daicel Chemical Industries, Ltd.).

Workup

  1. additionwere successively added
  2. concentrationconcentrated
  3. additionThe concentrate was diluted with ethyl acetate
  4. washwashed successively with dilute hydrochloric acid and saturated aqueous sodium hydrogencarbonate
  5. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product was purified by silica gel column chromatography (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-15167f7e39c34d6f8bcb2a85381016ae
Source dataset
uspto-grants-2000_02
Patent number
US06031111

Reaction notes

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