4-Methylmorpholine → (2-{2-(3,5-Dimethylphenyl)-5-[1-(methoxymethylcarbamoyl)-1-methyl-ethyl]-1H-indol-3-yl}ethyl)carbamic acid tert-butyl ester

HRID 1532384Notes

Reaction equation

HRID 1532384 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]([CH3:25])([CH3:24])[C:21](O)=[O:22])[CH:18]=2)[NH:13][C:12]=1[C:26]1[CH:31]=[C:30]([CH3:32])[CH:29]=[C:28]([CH3:33])[CH:27]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:35]1[C:39]2C=CC=CC=2N=N1.CN1CC[O:48][CH2:47]C1.CNOC.Cl.CN(C)CCCN=C=NCC>>[C:1]([O:5][C:6](=[O:7])[NH:8][CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20]([C:21](=[O:22])[NH:35][CH2:39][O:48][CH3:47])([CH3:25])[CH3:24])[CH:18]=2)[NH:13][C:12]=1[C:26]1[CH:27]=[C:28]([CH3:33])[CH:29]=[C:30]([CH3:32])[CH:31]=1)([CH3:2])([CH3:3])[CH3:4]

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 14232N,O-DimethylhydroxylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 154585232-[3-(2-tert-butoxycarbonylaminoethyl)-2-(3,5-dimethylphenyl)-1H-indol-5-yl]-2-methylpropionic acid

Product 1

HCID 56977920(2-{2-(3,5-Dimethylphenyl)-5-[1-(methoxymethylcarbamoyl)-1-methyl-ethyl]-1H-indol-3-yl}ethyl)carbamic acid tert-butyl ester

Procedure

To a suspension of 2-[3-(2-tert--butoxycarbonylamino-ethyl)-2-(3,5-dimethylphenyl)-1-H-indol-5-yl]-2-methylpropionic acid (1.23 g in 15 mL N,N-dimethylformamide) at 0° C. was added 608 mg of 1-hydroxybenzotriazole (HOBt), 0.48 mL 4-methylmorpholine and 352 mg of N,O-dimethylhydroxylamine hydrochlorideand the mixture stirred at low temperature. After 15 minutes, 826 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) were added and the mixture warmed to room temperature. The reaction was quenched after 3.5 days by concentration in vacuo, resuspending in ethyl acetate and washing sequentially with water, 0.3N sodium bisulfate, water, saturated sodium bicarbonate and brine. The organic portion was dried over sodium sulfate and the concentrate purified by flash chromatography on silica gel (hexane:ethyl acetate, 3:1) to give the title compound (905 mg).

Workup

  1. customThe reaction was quenched after 3.5 days by concentration in vacuo
  2. washwashing sequentially with water, 0.3N sodium bisulfate, water, saturated sodium bicarbonate and brine
  3. dry with materialThe organic portion was dried over sodium sulfate
  4. customthe concentrate purified by flash chromatography on silica gel (hexane:ethyl acetate, 3:1)

Sources & evidence

ORD record
ord-8e60b781271847b3ba5e7edcf555fdbe
Source dataset
uspto-grants-2001_03
Patent number
US06200957B1

Reaction notes

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