Hydrochloric Acid → (6RS,trans) 6-(1-methyl-4-piperidinylamino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2(1H)-one

HRID 1381094Notes

Reaction equation

HRID 1381094 reaction equation
[NH2:1][C@H:2]1[C@H:8]([OH:9])[C:7]2[CH:10]=[CH:11][CH:12]=[C:13]3[NH:14][C:15](=[O:16])[N:5]([C:6]=23)[CH2:4][CH2:3]1.[CH3:17][N:18]1[CH2:23][CH2:22][C:21](=O)[CH2:20][CH2:19]1.C([BH3-])#N.[Na+].Cl.[OH-].[Na+]>CO>[CH3:17][N:18]1[CH2:23][CH2:22][CH:21]([NH:1][C@H:2]2[C@H:8]([OH:9])[C:7]3[CH:10]=[CH:11][CH:12]=[C:13]4[NH:14][C:15](=[O:16])[N:5]([C:6]=34)[CH2:4][CH2:3]2)[CH2:20][CH2:19]1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 740491-Methyl-4-piperidoneHCID 5003444Sodium cyanoborohydrideHCID 59325228racemic trans 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,1-jk][1]-benzazepin-2[1H]-one

Product 1

HCID 86740744(6RS,trans) 6-(1-methyl-4-piperidinylamino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2(1H)-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of 7.6 g of (6RS,trans) 6-amino-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2(1H)-one, 7.6 ml of N-methyl-4-piperidone, 380 ml of methanol and 7.6 g of sodium cyanoborohydride was stirred at room temperature for 24 hours and after cooling to less than 0° C., 5 ml of concentrated hydrochloric acid were added thereto dropwise. The mixture was stirred at room temperature for 10 minutes and was cooled to 0° C. and adjusted to a pH of 8 by addition of sodium hydroxide. The methanol was evaporated and the residue was taken up in methylene chloride containing 10% methanol. The mixture was filtered and the filtrate was evaporated to dryness. The residue was chromatographed over silica gel and was eluted with an 80-15-5 ethyl acetate-methanol-ammonium hydroxide mixture to obtain 7.3 g of (6RS,trans) 6-(1-methyl-4-piperidinylamino)-7-hydroxy-4,5,6,7-tetrahydro-imidazo[4,5,l-j-k][1]-benzazepin-2(1H)-one. The said base was dissolved in 40 ml of ethanol and 20 ml of ethanolic hydrogen chloride were added thereto. The mixture was vacuum filtered to obtain 7 g of the dihydrochloride melting at ≃260° C.

Workup

  1. temperatureafter cooling to less than 0° C.
  2. stirringThe mixture was stirred at room temperature for 10 minutes
  3. temperaturewas cooled to 0° C.
  4. customThe methanol was evaporated
  5. filtrationThe mixture was filtered
  6. customthe filtrate was evaporated to dryness
  7. customThe residue was chromatographed over silica gel
  8. washwas eluted with an 80-15-5 ethyl acetate-methanol-ammonium hydroxide mixture

Sources & evidence

ORD record
ord-536e21d1e82b45fbb68f7d47367cdb23
Source dataset
uspto-grants-1986_04
Patent number
US04585770

Reaction notes

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