4-Methylmorpholine → HCID 86753454, compound

HRID 1458376Notes

Reaction equation

HRID 1458376 reaction equation
[C:1]([O:5][C:6]([N:8]([CH2:31][CH2:32][CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=1)[CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20](O)=[O:21])[CH:18]=2)[NH:13][C:12]=1[C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[CH:24]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O[N:42]1[C:46]2C=CC=CC=2N=N1.Cl.CN[O:54][CH3:55].Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>>[C:1]([O:5][C:6](=[O:7])[N:8]([CH2:9][CH2:10][C:11]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([C:20](=[O:21])[NH:42][CH2:46][O:54][CH3:55])[CH:18]=2)[NH:13][C:12]=1[C:23]1[CH:28]=[C:27]([CH3:29])[CH:26]=[C:25]([CH3:30])[CH:24]=1)[CH2:31][CH2:32][CH2:33][CH2:34][C:35]1[CH:40]=[CH:39][N:38]=[CH:37][CH:36]=1)([CH3:3])([CH3:4])[CH3:2]

Participants

6

Reactant 5

HCID 79724-MethylmorpholineHCID 757711-Hydroxybenzotriazole2×HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)2×HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride2×HCID 221008763-{2-[tert-butoxycarbonyl-(4-pyridin-4-yl-butyl)amino]ethyl}-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid

Product 1

HCID 86753454HCID 86753454, compoundYield 90.1%

Procedure

To a solution of 3-{2-[tert-butoxycarbonyl-(4-pyridin-4-yl-butyl)amino]ethyl}-2-(3,5-dimethylphenyl)-1H-indole-5-carboxylic acid (1.44 g in 25 mL N,N-dimethylformamide) at 0° C. was added 540 mg of 1-hydroxybenzotriazole (HOBt) followed by 0.44 mL 4-methylnorpholine and 365 mg N,O-dimethylhydroxylamine hydrochloride. After 15 minutes, 815 mg 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC) was added and the mixture allowed to warm to room temperature. After 3 days reaction time, an additional portion of 540 mg of HOBt, 0.44 mL 4-methylmorpholine, 365 mg N,O-dimethylhydroxylamine hydrochloride and 815 mg EDC were added. The reaction stopped after 4 days by concentration in vacuo and reconcentration from toluene to remove all volatiles. The residue was solvated in ethyl acetate and washed sequentially with saturated aqueous sodium bicarbonate and brine, then dried over sodium sulfate. Purification of the concentrate by flash chromatography on silica gel (hexane:ethyl acetate, 30:70; then 20:80; then 0:100) gave the title compound (1.4 g).

Workup

  1. customAfter 3 days reaction time
  2. concentrationThe reaction stopped after 4 days by concentration in vacuo and reconcentration from toluene
  3. customto remove all volatiles
  4. washwashed sequentially with saturated aqueous sodium bicarbonate and brine
  5. dry with materialdried over sodium sulfate
  6. customPurification of the
  7. concentrationconcentrate by flash chromatography on silica gel (hexane

Sources & evidence

ORD record
ord-50ef092968b14bb2a12713178dd11fed
Source dataset
uspto-grants-1998_12
Patent number
US05849764

Reaction notes

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