1,2-Dichloroethane → (S)-2-Isopropyl-11-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine dihydrochloride

HRID 131425Notes

Reaction equation

HRID 131425 reaction equation
[CH:1]([C:4]1[CH:28]=[CH:27][C:7]2[NH:8][C:9]3[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=3[N:11]=[C:12]([N:13]3[CH2:18][CH2:17][NH:16][C@@H:15]([CH2:19][CH2:20][O:21][CH3:22])[CH2:14]3)[C:6]=2[CH:5]=1)([CH3:3])[CH3:2].C=O.[C:31](O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+].[Cl:50]CCCl>>[ClH:50].[ClH:50].[CH:1]([C:4]1[CH:28]=[CH:27][C:7]2[NH:8][C:9]3[CH:26]=[CH:25][CH:24]=[CH:23][C:10]=3[N:11]=[C:12]([N:13]3[CH2:18][CH2:17][N:16]([CH3:31])[C@@H:15]([CH2:19][CH2:20][O:21][CH3:22])[CH2:14]3)[C:6]=2[CH:5]=1)([CH3:3])[CH3:2]

Participants

6

Reactant 5

HCID 111,2-DichloroethaneHCID 712FormaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 10249082(S)-2-Isopropyl-11-[3-(2-methoxy-ethyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine

Product 1

HCID 69214411(S)-2-Isopropyl-11-[3-(2-methoxy-ethyl)-4-methyl-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine dihydrochloride

Procedure

Combine (S)-2-isopropyl-11-[3-(2-methoxy-ethyl)-piperazin-1-yl]-5H-dibenzo[b,e][1,4]diazepine (0.405 g, 1.07 mmol) and 37% formaldehyde solution (0.1 mL, 1.12 mmol) in 1,2-dichloroethane (25 mL). Stir for 10 minutes and add sodium triacetoxy borohydride (0.343 g, 1.60 mmol). Stir an additional 30 minutes and then pour solution onto saturated sodium bicarbonate solution. Extract with methylene chloride to give 0.489 g of the crude product. Silica gel chromatography, eluting with methylene chloride:methanol (100:10), gives 0.354 g of the title compound as the free base. The dihydrochloride salt precipitates in ethyl acetate as a solid: mp=210° C.; mass spectrum (ion spray): m/z=393 (M+1); Analysis for C24H34Cl2N4O: calcd: C, 61.93; H, 7.36; N, 12.04; found: C, 61.74; H, 7.47; N, 11.86.

Workup

  1. stirringStir an additional 30 minutes
  2. extractionExtract with methylene chloride
  3. customto give 0.489 g of the crude product
  4. washSilica gel chromatography, eluting with methylene chloride:methanol (100:10)

Sources & evidence

ORD record
ord-c2882176fd9a4785b63d8dd037b2ea89
Source dataset
uspto-grants-2008_06
Patent number
US07384934B2

Reaction notes

Loading…