Hydrochloric Acid → 2,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(1-naphthalenylcarbonyl)-8-amino-1H-1,4-benzodiazepine, dihydrochloride

HRID 849389Notes

Reaction equation

HRID 849389 reaction equation
[ClH:1].Cl.[NH:3]1[CH:7]=[C:6]([CH2:8][N:9]2[C:15]3[CH:16]=[C:17]([N+:20]([O-])=O)[CH:18]=[CH:19][C:14]=3[CH2:13][N:12]([C:23]([C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)=[O:24])[CH2:11][CH2:10]2)[N:5]=[CH:4]1.[OH-].[Na+].C([O-])(O)=O.[Na+].Cl.Cl.Cl.N1C=C(CN2C3C=C(NC(=O)C)C=CC=3CN(C(C3C4C(=CC=CC=4)C=CC=3)=O)CC2)N=C1>CC(O)=O.O.CCOCC>[ClH:1].[ClH:1].[NH:3]1[CH:7]=[C:6]([CH2:8][N:9]2[C:15]3[CH:16]=[C:17]([NH2:20])[CH:18]=[CH:19][C:14]=3[CH2:13][N:12]([C:23]([C:25]3[C:34]4[C:29](=[CH:30][CH:31]=[CH:32][CH:33]=4)[CH:28]=[CH:27][CH:26]=3)=[O:24])[CH2:11][CH2:10]2)[N:5]=[CH:4]1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 516892Sodium BicarbonateHCID 178474025N-[2,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(1-naphthalenylcarbonyl)-1H-1,4-benzodiazepin-8-yl]acetamide, dihydrochlorideHCID 1784788782,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(1-naphthalenylcarbonyl)-8-nitro-1H-1,4-benzodiazepine, dihydrochloride

Product 1

HCID 1784786502,3,4,5-Tetrahydro-1-(1H-imidazol-4-ylmethyl)-4-(1-naphthalenylcarbonyl)-8-amino-1H-1,4-benzodiazepine, dihydrochloride

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 21899381Acetic acid--water (1/1)Solvent

Procedure

16% aqueous TiCl3 (2 mL) was added to a solution of Example 25 (0.10 g, 0.23 mmol) in AcOH/H2O (2 mL, 1:1). After stirring for 15 min, the reaction was made basic with 1N NaOH and NaHCO3 and stirred for 30 min. The layers were separated and the aqueous layer was reextracted with CHCl3 /CH3OH (9/1). The combined organic layers were dried over MgSO4, filtered and concentrated to afford 0.92 g. (73%) of Example 26. A 20 mg. sample of this material was treated with 1M HCl in ether (2 mL). A light yellow solid was formed which was triturated several times with ether and dried under vacuum to afford Example 26 (23 mg.) as a light yellow solid. (Example 26 is also Compound G of Example 22.)

Workup

  1. stirringstirred for 30 min
  2. customThe layers were separated
  3. dry with materialThe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customto afford 0.92 g
  7. customA light yellow solid was formed which
  8. customwas triturated several times with ether
  9. customdried under vacuum
  10. customto afford Example 26 (23 mg.) as a light yellow solid

Sources & evidence

ORD record
ord-39c59d78eb3e475e801df6ae0e82f595
Source dataset
uspto-grants-2000_01
Patent number
US06011029

Reaction notes

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