Cyanogen Bromide → 5-[6-[(4-tert-Butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]-1,3,4-oxadiazol-2-amine

HRID 1691455Notes

Reaction equation

HRID 1691455 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8]([S:11]([N:14]2[C:20]3[CH:21]=[C:22]([C:25]([NH:27][NH2:28])=[O:26])[CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:29]=[C:30]([C:33]([F:36])([F:35])[F:34])[CH:31]=[CH:32][C:16]=3[CH2:15]2)(=[O:13])=[O:12])=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([O-])(O)=O.[Na+].[N:42]#[C:43]Br>O1CCOCC1>[C:1]([C:5]1[CH:6]=[CH:7][C:8]([S:11]([N:14]2[C:20]3[CH:21]=[C:22]([C:25]4[O:26][C:43]([NH2:42])=[N:28][N:27]=4)[CH:23]=[CH:24][C:19]=3[NH:18][C:17]3[N:29]=[C:30]([C:33]([F:35])([F:36])[F:34])[CH:31]=[CH:32][C:16]=3[CH2:15]2)(=[O:13])=[O:12])=[CH:9][CH:10]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 10476Cyanogen BromideHCID 516892Sodium BicarbonateHCID 669016526-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbohydrazide2×

Product 1

HCID 596187325-[6-[(4-tert-Butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]-1,3,4-oxadiazol-2-amine

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a solution of 6-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbohydrazide (intermediate 57, 0.040 g, 0.0771 mmol) and NaHCO3 (7 mg in 0.187 mL of water) in dioxane (0.75 mL) was added cyanogen bromide (9 mg in 0.084 mL of dioxane) was in four equal portions over 5 min. After stirring at rt for 2 h, the reaction was quenched with saturated aqueous NaHCO3 and the product was extracted with EtOAc and DCM. The combined extracts were washed with brine, dried (MgSO4) and concentrated. The residue was purified by SiO2 column chromatography to provide the title compound. LC/MS: m/e 545.1 (M+H)+. 1H NMR (500 MHz, CD3OD): δ 7.78 (1H, s), 7,76 (1H, d, J=8.5 Hz), 7.67 (1H, d, J=3.6 Hz), 7.63 (1H, d, J=7.3 Hz), 7.07-7.13 (3H, m), 6.91 (1H, d, J=8.5 Hz), 4.6-4.9 (2H, br), 3.53 (3H, s), 1.22 (9H, s).

Workup

  1. customthe reaction was quenched with saturated aqueous NaHCO3
  2. extractionthe product was extracted with EtOAc and DCM
  3. washThe combined extracts were washed with brine
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customThe residue was purified by SiO2 column chromatography

Sources & evidence

ORD record
ord-c0c4ed62cc81458bb3a170283bf1522f
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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