(5-Methyl-1H-pyrazol-3-yl)[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]methanone → 1-(5-Methyl-1H-pyrazol-3-yl)-1-[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]ethanol

HRID 1691483Notes

Reaction equation

HRID 1691483 reaction equation
[CH3:1][C:2]1[NH:6][N:5]=[C:4]([C:7]([C:9]2[CH:10]=[CH:11][C:12]3[NH:18][C:17]4[N:19]=[C:20]([C:23]([F:26])([F:25])[F:24])[CH:21]=[CH:22][C:16]=4[CH2:15][N:14]([S:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=4)(=[O:29])=[O:28])[C:13]=3[CH:41]=2)=[O:8])[CH:3]=1.I[C:43]1C=CC2NC3N=C(C(F)(F)F)C=CC=3CN(S(C3C=CC(OC(F)(F)F)=CC=3)(=O)=O)C=2C=1.C([Mg]Cl)(C)C.CON(C)C(C1C=C(C)NN=1)=O>C1COCC1.C1(C)C=CC=CC=1>[CH3:1][C:2]1[NH:6][N:5]=[C:4]([C:7]([C:9]2[CH:10]=[CH:11][C:12]3[NH:18][C:17]4[N:19]=[C:20]([C:23]([F:24])([F:25])[F:26])[CH:21]=[CH:22][C:16]=4[CH2:15][N:14]([S:27]([C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:39])([F:40])[F:38])=[CH:32][CH:31]=4)(=[O:29])=[O:28])[C:13]=3[CH:41]=2)([OH:8])[CH3:43])[CH:3]=1

Participants

7

Reactant 4

HCID 59618680(5-Methyl-1H-pyrazol-3-yl)[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]methanoneHCID 596187318-Iodo-6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine2×HCID 59618740N-methoxy-N,3-dimethyl-1H-pyrazole-5-carboxamideHCID 178418918HCID 178418918, compound

Product 1

HCID 596186281-(5-Methyl-1H-pyrazol-3-yl)-1-[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]ethanol

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

(5-Methyl-1H-pyrazol-3-yl)[6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-8-yl]methanone To a solution of 8-iodo-6-{[4-(trifluoromethoxy)phenyl]sulfonyl}-2-(trifluoromethyl)-6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepine (950 mg, 1.544 mmol, intermediate 61) in 5 ml of THF was added a solution of isopropyl magnesium chloride (3.47 ml, 6.95 mmol) in THF (2M) at 0° C. The solution was stirred at 0° C. for 30 min, then a mixture of N-methoxy-N,5-dimethyl-1H-pyrazole-3-carboxamide (261 mg, 1.544 mmol) in 3 mL of toluene was added. The reaction mixture was stirred for 2 hr at 0° C. and then allowed to warm to rt overnight. The reaction was quenched by the addition of 4 mL of 0.5 N HCl. The resulting viscous residue was washed with ethyl acetate (30 mL×2) and acetone (20 mL×2). The combined washes were evaporated under reduced pressure and the residue was crystallized from CH2Cl2 to give the title compound as a light yellow solid; Mass Spectrum: m/e=598 (M+1).

Workup

  1. additionwas added
  2. stirringThe reaction mixture was stirred for 2 hr at 0° C.
  3. temperatureto warm to rt overnight
  4. customThe reaction was quenched by the addition of 4 mL of 0.5 N HCl
  5. washThe resulting viscous residue was washed with ethyl acetate (30 mL×2) and acetone (20 mL×2)
  6. customThe combined washes were evaporated under reduced pressure
  7. customthe residue was crystallized from CH2Cl2

Sources & evidence

ORD record
ord-df965961dd7c43efb5cd26c9d75dece3
Source dataset
uspto-grants-2012_04
Patent number
US08153626B2

Reaction notes

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