Hydrochloric Acid → HCID 54046228, compound

HRID 2372310Notes

Reaction equation

HRID 2372310 reaction equation
[N:1]1[C:2](=[O:12])[CH:3]=[CH:4][CH:5]=[C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][C:7]=12.[H-].[Na+].Cl[CH2:16][C:17]#[N:18].Cl>CN(C=O)C.CCOC(C)=O>[C:17]([CH2:16][N:1]1[C:2](=[O:12])[CH2:3][CH2:4][C:5]2[CH:6]=[CH:11][CH:10]=[CH:9][C:8]=2[CH:7]1[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)#[N:18]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 7856Chloroacetonitrile2×HCID 24758Sodium hydride2×HCID 20244764HCID 20244764, compound

Product 1

HCID 54046228HCID 54046228, compoundYield 190.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1.80 g of the benzazepinone of Example 1 (7.6 mmol) in 15 mL of DMF was added 13 mg of KI (0.76 mmol, 0.01 eq.) and 200 mg of NaH (8.4 mmol, 1.1 eq.). After 1 hr at 25°, 0.58 mL of ClCH2CN (9.2 mmol, 1.2 eq.) was added, causing a dark red solution to form. After 24 hr an additional 200 mg of NaH (8.4 mmol, 1.1 eq.) and 0.58 mL of ClCH2CN (9.2 mmol, 1.2 eq.) were added. After a further 8 hr, 150 mL 0.5N of HCl was added, followed by 150 mL of EtOAc. The EtOAc layer was then washed with saturated NaCl (2×150 mL), dried (Na2SO4), and the solvents evaporated to yield 2.0 g of crude 2-cyanomethyl-1-phenyl-1,2,4,5-tetrahydro-2 (3H)benzazepin-3-one as a red oil. This oil was immediately dissolved in 60 mL of glacial HOAc, 0.5% of 10% Pd/C was added, and the resulting mixture was hydrogenated for 4 hr at 50 psi. An additional 0.5 g of 10% Pd/C was added and the mixture hydrogenated a further 4 hr at 50 psi. The reaction mixture was filtered through celite, the filtrate evaporated, and the residue partitioned between 2N NaOH and EtOAc. The organic phase was washed with saturated NaCl, dried (Na2SO4), and evaporated to yield 0.40 g of crude 2-(2-aminoethyl compound as a yellow oil. This oil was immediately dissolved in 60 mL of PhCH3, 50 mg of p-TSA was added, and the resulting mixture refluxed for 24hr with a Dean-Stark water separator. The reaction mixture was cooled to 25° , the volatiles were removed in vacuo, and the residue partitioned between saturated NaHCO3 and EtOAc. The EtOAc layer was washed with saturated NaCl, dried (Na2SO4), and evaporated to yield 383 mg of 10-phenyl-1,2,4,5-tetrahydro-10H-imidazo[1,2-b]benzazepine free base (19%) as a viscous yellow oil. Conversion to the hydrochloride salt (EtOH/ethanolic HCl) produced as white amorphous solid, mp ~150° (dec.).

Workup

  1. customto form
  2. waitAfter a further 8 hr
  3. washThe EtOAc layer was then washed with saturated NaCl (2×150 mL)
  4. dry with materialdried (Na2SO4)
  5. customthe solvents evaporated

Sources & evidence

ORD record
ord-5e5f4a8a8148470fbe8685740926365e
Source dataset
uspto-grants-1992_03
Patent number
US05098901

Reaction notes

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