Chloroform → (R)-7-Cyano-2,3,4,5-tetrahydro-1-[(1-methyl-1H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3-(phenylmethyl)-1H-1,4-benzodiazepine, monohydrochloride

HRID 849403Notes

Reaction equation

HRID 849403 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:12]([CH2:13][C:14]3[N:15]=[CH:16][N:17](C(OC(C)(C)C)=O)[CH:18]=3)[CH2:11][C@@H:10]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[N:9]([S:33]([CH3:36])(=[O:35])=[O:34])[CH2:8][C:7]=2[CH:37]=1)#[N:2].O(C)S([C:42](F)(F)F)(=O)=O.CCN(C(C)C)C(C)C.C(Cl)(Cl)[Cl:57]>C(Cl)Cl>[ClH:57].[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[N:12]([CH2:13][C:14]3[N:15]([CH3:42])[CH:16]=[N:17][CH:18]=3)[CH2:11][C@@H:10]([CH2:26][C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[N:9]([S:33]([CH3:36])(=[O:34])=[O:35])[CH2:8][C:7]=2[CH:37]=1)#[N:2]

Participants

6

Reactant 4

HCID 6212ChloroformHCID 9526Methyl triflateHCID 81531DiisopropylethylamineHCID 69841490(R)-7-cyano-2,3,4,5-tetrahydro-1-[(((1,1-dimethylethoxy)-carbonyl)-1H-imidazol-4-yl)methyl]-4-(methylsulfonyl)-3-(phenylmethyl)-1H-1,4-benzodiazepine2×

Product 1

HCID 131721583(R)-7-Cyano-2,3,4,5-tetrahydro-1-[(1-methyl-1H-imidazol-5-yl)methyl]-4-(methylsulfonyl)-3-(phenylmethyl)-1H-1,4-benzodiazepine, monohydrochlorideYield 74%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 200 mg (0.38 mmol) of (R)-7-cyano-2,3,4,5-tetrahydro-1-[(((1,1-dimethylethoxy)-carbonyl)-1H-imidazol-4-yl)methyl]-4-(methylsulfonyl)-3-(phenylmethyl)-1H-1,4-benzodiazepine (prepared from Example 224 as described for Compound A of Example 225) in 2 mL of methylene chloride, at -78° C. and under argon, was added dropwise 59 μL (0.48 mmol) of methyl triflate. The reaction was allowed to warm to rt, during which time a white precipitate was obtained. Stirring was continued at rt for 3 hr, after which time 140 μL (0.8 mmol) of DIEA was added and stirring continued overnight at rt. The mixture, without workup, was subjected to flash chromatography on a 30 cc column of silica gel. Elution with 2% MeOH--CHCl3 afforded 122 mg (0.28 mmol, 74%) of a clear colorless oil which crystallized on standing. This material was converted to its hydrochloride by the addition of 0.28 mL of 1M HCl in ether to a methylene chloride solution (2 mL) of the free base. A white precipitate was obtained which on filtration afforded 90 mg of Example 235 as a white powder.

Workup

  1. customwas obtained
  2. stirringstirring continued overnight at rt
  3. washElution with 2% MeOH

Sources & evidence

ORD record
ord-95efa60ac0f6485181492f982e65eb76
Source dataset
uspto-grants-2000_01
Patent number
US06011029

Reaction notes

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