Methylamine → E-2110 free base

HRID 1640066Notes

Reaction equation

HRID 1640066 reaction equation
[CH3:1][O:2][C:3]1[C:12]([CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]([OH:32])=O)[CH:28]=4)[CH:23]=[CH:22]3)[CH2:17][CH2:16]2)=[C:11]2[C:6]([C:7](=[O:35])[CH2:8][C:9]([CH3:34])([CH3:33])[O:10]2)=[CH:5][CH:4]=1.[C:36](N1C=CN=C1)([N:38]1C=CN=C1)=O.CN.C(OCC)(=O)C>C(O)C.O>[CH3:1][O:2][C:3]1[C:12]([CH2:13][CH2:14][N:15]2[CH2:20][CH2:19][CH:18]([N:21]3[C:29]4[C:24](=[CH:25][CH:26]=[C:27]([C:30]([NH:38][CH3:36])=[O:32])[CH:28]=4)[CH:23]=[CH:22]3)[CH2:17][CH2:16]2)=[C:11]2[C:6]([C:7](=[O:35])[CH2:8][C:9]([CH3:33])([CH3:34])[O:10]2)=[CH:5][CH:4]=1

Participants

7

Reactant 4

HCID 6329MethylamineHCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 594394671-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylic acid

Product 1

HCID 11677552E-2110 free base

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
40 °C

Procedure

1.0 g of 1-{1-[2-(7-methoxy-2,2-dimethyl-4-oxochroman-8-yl)ethyl]piperidin-4-yl}-1H-indole-6-carboxylic acid was dissolved in 25 mL of ethanol, added with 851 mg of 1,1′-cabonyldiimidazole and the reaction mixture was stirred at 40° C. for 2 hours. The reaction mixture was cooled with an ice-water bath, added 1.81 mL of 40% methylamine aqueous solution thereto and stirred for 50 minutes. The reaction mixture was added with 40 mL of ethyl acetate and 20 mL of water and the organic layer was separated. The organic layer was washed with 20 mL of 10% sodium chloride solution and added with 8.5 mL of 1 N hydrochloric acid to adjust the pH to 7. The aqueous layer was discarded and the organic layer was washed with 10 mL of water. The organic layer was concentrated in vacuo, added with 3 mL of 1-propanol and concentrated again and the title compound was obtained.

Workup

  1. temperatureThe reaction mixture was cooled with an ice-water bath
  2. stirringstirred for 50 minutes
  3. customthe organic layer was separated
  4. washThe organic layer was washed with 20 mL of 10% sodium chloride solution
  5. additionadded with 8.5 mL of 1 N hydrochloric acid
  6. washthe organic layer was washed with 10 mL of water
  7. concentrationThe organic layer was concentrated in vacuo
  8. additionadded with 3 mL of 1-propanol
  9. concentrationconcentrated again

Sources & evidence

ORD record
ord-d03f264660204507a17eec4dededf7ca
Source dataset
uspto-grants-2012_02
Patent number
US08110688B2

Reaction notes

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