Water → HCID 25134213, compound

HRID 1184650Notes

Reaction equation

HRID 1184650 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].[CH2:33]([O:40][P:41]([O:59][CH2:60][C:61]1[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1)([O:43][C:44]1[CH:49]=[C:48]([CH3:50])[CH:47]=[C:46]([CH3:51])[C:45]=1[C:52]([CH3:58])([CH3:57])[CH2:53][C:54](O)=[O:55])=[O:42])[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1.Cl.C(N=C=NCCCN(C)C)C.O>CN(C)C1C=CN=CC=1.ClCCl>[CH2:60]([O:59][P:41]([O:40][CH2:33][C:34]1[CH:35]=[CH:36][CH:37]=[CH:38][CH:39]=1)([O:43][C:44]1[CH:49]=[C:48]([CH3:50])[CH:47]=[C:46]([CH3:51])[C:45]=1[C:52]([CH3:58])([CH3:57])[CH2:53][C:54]([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:55])=[O:42])[C:61]1[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=1

Participants

7

Reactant 4

HCID 962WaterHCID 216237TolvaptanHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 10600827HCID 10600827, compound

Product 1

HCID 25134213HCID 25134213, compoundYield 71.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

Tolvaptan (0.63 g), 3-[2-(bis-benzyloxy-phosphoryloxy)-4,6-dimethyl-phenyl]-3-methyl-butyric acid (0.70 g), and 4-dimethylaminopyridine (DMAP) (24 mg, 0.22 mmol) were suspended in dichloromethane (10 ml). N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (WSC) (383 mg) was added thereto, and the mixture was stirred at room temperature for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate, 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→35:65). The purified product was concentrated under reduced pressure to obtain 0.92 g of 7-chloro-1-[2-methyl-4-(2-methyl-benzoylamino)-benzoyl]-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl 3-[2-(bis-benzyloxy-phosphoryloxy)-4,6-dimethyl-phenyl]-3-methyl-butyrate as white amorphous solid.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationAfter filtration and concentration under reduced pressure
  4. customthe residue was purified by silica gel flash chromatography (n-hexane:ethyl acetate=70:30→35:65)
  5. concentrationThe purified product was concentrated under reduced pressure

Sources & evidence

ORD record
ord-6d280e4af6da4da9aa4f67be42eefc80
Source dataset
uspto-grants-2014_03
Patent number
US08669229B2

Reaction notes

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