Sodium Hydroxide → HCID 21265960, compound

HRID 566274Notes

Reaction equation

HRID 566274 reaction equation
[OH-:1].[Na+].[Cl:3][C:4]1[S:13][C:12]2[N:11]3[CH2:14][C:15]([CH2:18]Cl)(O)[N:16]=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:6]=2[CH:5]=1>>[Cl:3][C:4]1[S:13][C:12]2[N:11]3[CH2:14][CH:15]([CH2:18][OH:1])[N:16]=[C:10]3[CH2:9][N:8]=[C:7]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[F:26])[C:6]=2[CH:5]=1

Participants

3

Reactant 2

HCID 14798Sodium Hydroxide2×HCID 21265981HCID 21265981, compound

Product 1

HCID 21265960HCID 21265960, compound

Procedure

37.2 g of 2.5N sodium hydroxide solution were added at 60° C. to a suspension of the reaction mixture (RS)-2-chloro-8-chloromethyl-4-(2-fluoro-phenyl)-8,9-dihydro-6H-imidazo[1,2-a]thieno[3,2-f][1,4]diazepin-8-ol obtained in accordance with paragraph e) and stirred under argon for 21 h., subsequently two 18.7 g portions of 2.5N sodium hydroxide solution were added at intervals of two hours and the mixture was stirred for 2 h. The suspension was extracted with sodium chloride solution saturated with dichloro methane in the presence of a small amount of methanol. The dichloromethane extracts were dried with sodium sulphate, filtered and evaporated to dryness in a vacuum. After crystallization of the residue from 5% methanol in dichloromethane 3.3 g of the starting product of step e) were recovered. The mother liquors were evaporated to dryness in a vacuum and the residue was chromatographed on 800 g of silica gel. With 5% methanol in dichloromethane there were eluted 1.5 g of 2-chloro-4-(2-fluoro-phenyl)-8,9-dihydro-6 6H-imidazo[1,2-a]thieno-[3,2-f][1,4]diazepine-8-methanol which was used without further purification as the starting product for the step described below.

Workup

  1. customobtained in accordance with paragraph e) and
  2. stirringthe mixture was stirred for 2 h
  3. extractionThe suspension was extracted with sodium chloride solution saturated with dichloro methane in the presence of a small amount of methanol
  4. dry with materialThe dichloromethane extracts were dried with sodium sulphate
  5. filtrationfiltered
  6. customevaporated to dryness in a vacuum
  7. customAfter crystallization of the residue from 5% methanol in dichloromethane 3.3 g of the starting product of step e)
  8. customwere recovered
  9. customThe mother liquors were evaporated to dryness in a vacuum
  10. customthe residue was chromatographed on 800 g of silica gel
  11. washWith 5% methanol in dichloromethane there were eluted 1.5 g of 2-chloro-4-(2-fluoro-phenyl)-8,9-dihydro-6 6H-imidazo[1,2-a]thieno-[3,2-f][1,4]diazepine-8-methanol which
  12. customwas used without further purification as the starting product for the step

Sources & evidence

ORD record
ord-5a881066eef24ae8b389764666ef6529
Source dataset
uspto-grants-2001_01
Patent number
US06174881B1

Reaction notes

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