Ammonium Hydroxide → HCID 178477930, compound

HRID 849398Notes

Reaction equation

HRID 849398 reaction equation
CC(C)(OC(N1CC2C=C(C3C=CC=CC=3)C=CC=2NCC1)=O)C.[ClH:25].[NH:26]1[CH:30]=[C:29]([CH2:31][N:32]2[C:38]3[CH:39]=[CH:40][C:41]([C:43]4[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=4)=[CH:42][C:37]=3[CH2:36][N:35](C(C3C4C(=CC=CC=4)C=CC=3)=O)[CH2:34][CH2:33]2)[N:28]=[CH:27]1.C1(C(N2C3C=CC=CC=3CNCC2)=O)C2C(=CC=CC=2)C=CC=1.C(C1N=CNC=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+].[OH-].[NH4+]>C(Cl)Cl.C(O)(=O)C>[ClH:25].[NH:26]1[CH:30]=[C:29]([CH2:31][N:32]2[C:38]3[CH:39]=[CH:40][C:41]([C:43]4[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=4)=[CH:42][C:37]=3[CH2:36][NH:35][CH2:34][CH2:33]2)[N:28]=[CH:27]1

Participants

10

Reactant 7

HCID 14923Ammonium HydroxideHCID 764281H-Imidazole-4-carbaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 105662832,3,4,5-Tetrahydro-1-(1-naphthalenylcarbonyl)-1h-1,4-benzodiazepineHCID 108298392,3,4,5-Tetrahydro-4-[(1,1-dimethylethoxy)-carbonyl]-7-phenyl-1h-1,4-benzodiazepineHCID 178479668HCID 178479668, compound

Product 1

HCID 178477930HCID 178477930, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 2,3,4,5-tetrahydro-4-[(1,1-dimethylethoxy)-carbonyl]-7-phenyl-1H-1,4-benzodiazepine (prepared from Compound B of Example 12 as described for Compound A of Example 4, 0.20 g) and 4-formyl imidazole (0.52 g, 5.6 mmol) in CH2Cl2 (10 mL) and acetic acid (2 mL) was stirred for 40 min. Sodium triacetoxyborohydride (0.9 g, 6 mmol) was added and stirring was continued for 4 hrs. Sodium bicarbonate (sat., 5 mL) and ammonium hydroxide (conc, 5 mL) were added and the mixture was stirred for another 3 hrs. The aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic layers were washed with 1N NaOH (2×10 mL) and conc. NH4OH (10 mL), dried (Na2SO4) and evaporated. The residual solid was stirred in MeOH (5 mL) and aqueous HCl in dioxane (4M, 10 mL) overnight. The solvent was evaporated and the residue was triturated with CHCl3 to give a solid (0.35 g) which was purified by preparative HPLC (methanolwater gradient with 0.1% TFA) and converted to the HCl salt by lyophilization from 1M HCl (5 mL) to provide Example 89 (0.12 g, 57%) as an off white solid.

Workup

  1. stirringthe mixture was stirred for another 3 hrs
  2. extractionThe aqueous layer was extracted with CH2Cl2 (3×50 mL)
  3. washThe combined organic layers were washed with 1N NaOH (2×10 mL) and conc. NH4OH (10 mL)
  4. dry with materialdried (Na2SO4)
  5. customevaporated
  6. stirringThe residual solid was stirred in MeOH (5 mL)
  7. customaqueous HCl in dioxane (4M, 10 mL) overnight
  8. customThe solvent was evaporated
  9. customthe residue was triturated with CHCl3

Sources & evidence

ORD record
ord-de2f9ec3a0954174a7b6360d98b0b2a2
Source dataset
uspto-grants-2000_01
Patent number
US06011029

Reaction notes

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