Hydrochloric Acid → HCID 131717916, compound

HRID 248830Notes

Reaction equation

HRID 248830 reaction equation
Cl.[NH2:2][CH2:3][CH2:4][C:5]([NH:7][CH2:8][C:9]([N:11]1[CH2:17][C:16]2[CH:18]=[CH:19][CH:20]=[CH:21][C:15]=2[O:14][C:13]2[CH:22]=[CH:23][C:24]([Cl:26])=[CH:25][C:12]1=2)=[O:10])=[O:6].[OH-].[K+].[S:29]1[CH:33]=[CH:32][CH:31]=[C:30]1[CH:34]=O.C([BH3-])#N.[Na+].Cl>CO.C(O)(=O)C>[ClH:26].[Cl:26][C:24]1[CH:23]=[CH:22][C:13]2[O:14][C:15]3[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=3[CH2:17][N:11]([C:9](=[O:10])[CH2:8][NH:7][C:5](=[O:6])[CH2:4][CH2:3][NH:2][CH2:34][C:30]3[S:29][CH:33]=[CH:32][CH:31]=3)[C:12]=2[CH:25]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 73642-ThiophenecarboxaldehydeHCID 14797Potassium HydroxideHCID 5003444Sodium cyanoborohydrideHCID 131717915HCID 131717915, compound

Product 1

HCID 131717916HCID 131717916, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 887MethanolSolvent2×

Procedure

A mixture of 3-amino-N-[2-(8-chloro-10,11-dihydrodibenz[b,f][1,4]-oxazepin-10-yl)-2-oxoethyl]-propanamide, monohydrochloride (2.00 grams) in methanol (160 mL) and potassium hydroxide (0.38 gram) was stirred at room temperature until a solution formed. To this was added a solution of thiophene-2-carboxaldehyde (0.62 gram) in methanol (20 mL), and the solution was stirred at room temperature under a nitrogen atmosphere for 4 hours. To the solution was then added sodium cyanoborohydride (0.46 gram), and the pH of the reaction was adjusted to approximately 6 with acetic acid. The reaction was stirred at room temperature under a nitrogen atmosphere for 48 hours, made acidic to pH 2 with 2 N HCl, and evaporated in vacuo. The residue was suspended in water (150 mL), made basic to pH 11 with 1N NaOH, and extracted with chloroform (150 mL, and then 2×100 mL). The combined chloroform extracts were washed with 1N NaOH (2×100 mL), water (100 mL) and brine (150 mL), dried over MgSO4, and evaporated in vacuo. The crude product was purified by flash chromatography through silica gel 60 (350 mL) using 95:5 chloroform:ethanol (3A). The purified product was taken up in absolute ethanol (20 mL), cooled in an ice water bath, and acidified with 9.5 M HCl in ethanol (1.5 mL). After several minutes, the solution was evaporated in vacuo, and the resulting foam was dried in vacuo at 56° C. The yield of the title compound was 0.79 gram (32%). Analysis calculated for C23H22ClN3O3S×1 HCl: C, 56.10; H, 4,71; N, 8.53; Cl, 14.40; S, 6.51 Found: C, 55.74; H, 4.72; N, 8.47; Cl, 14.51; S, 6.49.

Workup

  1. customformed
  2. stirringthe solution was stirred at room temperature under a nitrogen atmosphere for 4 hours
  3. stirringThe reaction was stirred at room temperature under a nitrogen atmosphere for 48 hours
  4. customevaporated in vacuo
  5. extractionextracted with chloroform (150 mL
  6. washThe combined chloroform extracts were washed with 1N NaOH (2×100 mL), water (100 mL) and brine (150 mL)
  7. dry with materialdried over MgSO4
  8. customevaporated in vacuo
  9. customThe crude product was purified by flash chromatography through silica gel 60 (350 mL)
  10. temperaturecooled in an ice water bath
  11. waitAfter several minutes
  12. customthe solution was evaporated in vacuo
  13. customthe resulting foam was dried in vacuo at 56° C

Sources & evidence

ORD record
ord-d0287ecbde8349ce8293ba5795a24adf
Source dataset
uspto-grants-1993_05
Patent number
US05212169

Reaction notes

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