Phosgene → HCID 66901645, compound

HRID 1691452Notes

Reaction equation

HRID 1691452 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:37](Cl)(Cl)=[O:38]>C(Cl)Cl.C1(C)C=CC=CC=1>[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:37](=[O:38])[NH: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 2

HCID 6371PhosgeneHCID 669016526-[(4-tert-butylphenyl)sulfonyl]-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine-8-carbohydrazide2×

Product 1

HCID 66901645HCID 66901645, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-20 °C

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) in DCM (0.2 mL) at −78° C. was added phosgene (0.081 mL of a ˜20% solution in toluene) dropwise. After stirring at −20° C. overnight, 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 via SiO2 column chromatography, eluting with mixtures of EtOAc and hexane, to afford the title compound. LC/MS: m/e 546.1 (M+H)+. 1H NMR (500 MHz, CDCl3): δ 7.96 (1H, d, J=6.4 Hz), 7.62 (11-1, d, J=8.4 Hz), 7.54 (1H, d, J=7.8 Hz), 7.29 (1H, d, J=5.5 Hz), 7.03-7.04 (3H, m), 6.86-6.89 (3H, m), 4.50-4.90 (2H, br), 1.14 (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 via SiO2 column chromatography
  7. washeluting with mixtures of EtOAc and hexane

Sources & evidence

ORD record
ord-192eced1fa1c472f873619d2ffcdbf7b
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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