Pyridine → HCID 66733393, compound

HRID 1519474Notes

Reaction equation

HRID 1519474 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][C:7]=1[C:8]([NH:10][C:11]1[CH:12]=[CH:13][C:14]([C:18]([N:20]2[C:26]3[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]=3[CH:24]([OH:32])[CH2:23][CH2:22][CH2:21]2)=[O:19])=[C:15]([CH3:17])[CH:16]=1)=[O:9].N1C=CC=CC=1.Cl[C:40]([O:42][CH2:43][Cl:44])=[O:41]>ClCCl>[C:40](=[O:41])([O:32][CH:24]1[CH2:23][CH2:22][CH2:21][N:20]([C:18](=[O:19])[C:14]2[CH:13]=[CH:12][C:11]([NH:10][C:8](=[O:9])[C:7]3[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=3[CH3:1])=[CH:16][C:15]=2[CH3:17])[C:26]2[CH:27]=[CH:28][C:29]([Cl:31])=[CH:30][C:25]1=2)[O:42][CH2:43][Cl:44]

Participants

5

Reactant 3

HCID 1049PyridineHCID 62754Chloromethyl chloroformateHCID 216237Tolvaptan

Product 1

HCID 66733393HCID 66733393, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Tolvaptan (5.0 g) and pyridine (1.1 ml) were suspended in dichloromethane (50 ml). Chloromethyl chloroformate (1.1 ml) was added thereto under cooling with ice, and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was washed with water, dried over anhydrous sodium sulfate. After filtration and concentration under reduced pressure, the residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=70:30→50:50). The purified product was concentrated under reduced pressure to obtain 6.1 g of chloromethyl {7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl} carbonate as white amorphous solid.

Workup

  1. temperatureunder cooling with ice
  2. washThe reaction mixture was washed with water
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationAfter filtration and concentration under reduced pressure
  5. customthe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=70:30→50:50)
  6. concentrationThe purified product was concentrated under reduced pressure

Sources & evidence

ORD record
ord-ea11afe405f4423582aebe1afb4f39e9
Source dataset
uspto-grants-2015_07
Patent number
US09073868B2

Reaction notes

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