Sodium Hydroxide → 1-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-ethyoxyethyl)-1H-benzimidazol-2-yl) 1,4 diazepan-1-yl)ethyl)-3-(3,4-dichlorophenyl)pyrrolidine

HRID 637023Notes

Reaction equation

HRID 637023 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)([CH2:13][CH:14]=O)[CH2:9]1)=[O:7].[CH2:31]([O:33][CH2:34][CH2:35][N:36]1[C:40]2[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=2[N:38]=[C:37]1[N:45]1[CH2:51][CH2:50][CH2:49][NH:48][CH2:47][CH2:46]1)[CH3:32].C([BH3-])#N.[Na+].[OH-].[Na+]>CO.C(OCC)(=O)C.CO.ClCCl>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[C:6]([N:8]1[CH2:12][CH2:11][C:10]([CH2:13][CH2:14][N:48]2[CH2:49][CH2:50][CH2:51][N:45]([C:37]3[N:36]([CH2:35][CH2:34][O:33][CH2:31][CH3:32])[C:40]4[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=4[N:38]=3)[CH2:46][CH2:47]2)([C:16]2[CH:21]=[CH:20][C:19]([Cl:22])=[C:18]([Cl:23])[CH:17]=2)[CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 9984168Emedastine EP Impurity EHCID 184649301-(3,4,5-Trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-oxoethyl)pyrrolidine

Product 1

HCID 184646031-(3,4,5-Trimethoxybenzoyl)-3-(2-(4-(1-(2-ethyoxyethyl)-1H-benzimidazol-2-yl) 1,4 diazepan-1-yl)ethyl)-3-(3,4-dichlorophenyl)pyrrolidine

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 21584119Ethylacetate methanolSolvent

Procedure

Combine 1-(3,4,5-trimethoxybenzoyl)-3-(3,4-dichlorophenyl)-3-(2-oxoethyl)pyrrolidine (0.51 g, 1.13 mmol), 4-(1-(2-ethoxyethyl)-1H-benzimidazol-2-yl)[1,4]diazepane (0.40 g, 1.36 mmol), and silica gel (about 2 g) in methanol (24 mL) and stir. After 3 days, add sodium cyanoborohydride (0.71 g, 11.3 mmol) and 3 Å molecular sieves (about 12 g) and stir under an inert atmosphere. After 18 hours, add a solution of 2 M sodium hydroxide and dichloromethane and stir. After 18 hours, filter, separate the layers in the filtrate, and extract the organic layer with brine. Dry the organic layer over Na2SO4, filter, and evaporate in vacuo to give a residue. Chromatograph the residue on silica gel eluting with 1/1 ethyl acetate/methanol to give, after drying in vacuo at 82° C., the title compound: mp; 55-65° C. Rf=0.36 (silica gel, 1/1 ethyl acetate/methanol). Elemental Analysis calculated for C38H47Cl2N5O5: C 62.98; H 6.54; N 9.66; Found: C 62.65; H 6.65; N 9.51.

Workup

  1. waitAfter 18 hours
  2. stirringstir
  3. waitAfter 18 hours
  4. filtrationfilter
  5. customseparate the layers in the filtrate
  6. extractionextract the organic layer with brine
  7. dry with materialDry the organic layer over Na2SO4
  8. filtrationfilter
  9. customevaporate in vacuo
  10. customto give a residue
  11. customafter drying in vacuo at 82° C.

Sources & evidence

ORD record
ord-0f3aa4b3cc4742d8bb945d6182e18f51
Source dataset
uspto-grants-2001_02
Patent number
US06194406B1

Reaction notes

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