Methylhydrazine → 5-(5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-(4-chlorophenyl)-1,3-dimethyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873906Notes

Reaction equation

HRID 873906 reaction equation
[C:1]([C:4]1[CH:5]([C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[N:6]([C:11]2[CH:12]=[C:13]([Cl:19])[C:14](=[O:18])[N:15]([CH3:17])[CH:16]=2)[C:7](=[O:10])[C:8]=1O)(=O)[CH3:2].[CH3:27][NH:28][NH2:29]>CC(O)=O.CCOCC.C(Cl)Cl>[Cl:19][C:13]1[C:14](=[O:18])[N:15]([CH3:17])[CH:16]=[C:11]([N:6]2[CH:5]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[C:4]3[C:1]([CH3:2])=[N:29][N:28]([CH3:27])[C:8]=3[C:7]2=[O:10])[CH:12]=1

Participants

5

Reactant 2

HCID 6061MethylhydrazineHCID 1177027635-(3-acetyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)-3-chloro-1-methyl-pyridin-2(1H)-one

Product 1

HCID 862920005-(5-chloro-1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4-(4-chlorophenyl)-1,3-dimethyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-oneYield 20%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 21881112Ethyl ether methylene chlorideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 5-(3-acetyl-2-(4-chlorophenyl)-4-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl)-3-chloro-1-methylpyridin-2(1H)-one (Step 57.1) (300 mg, 0.763 mmol) in AcOH (5 mL) was added methyl hydrazine (0.201 mL, 3.81 mmol) and the reaction mixture was stirred for 18 hr at 100° C. The reaction mixture was concentrated under reduced pressure, quenched with a saturated aq. NaHCO3 solution and extracted with CH2Cl2). The combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The crude product was purified by silica gel column chromatography eluting with EtOAc. Trituration in Et2O/CH2Cl2 (9:1) afforded the title product (60 mg, 0.149 mmol, 20% yield) as white solid. tR: 4.05 min (HPLC 1); tR: 0.95 min (LC-MS 2); ESI-MS: 403/405 [M+H]+ (LC-MS 2); Rf=0.24 (EtOAc); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.89 (s, 3H) 3.41 (s, 3H) 3.89 (s, 3H) 6.07 (s, 1H) 7.26 (d, J=8.2 Hz, 2H) 7.35 (d, J=8.2 Hz, 2H) 7.86 (d, J=2.0 Hz, 1H) 7.90 (d, J=2.3 Hz, 1H).

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. customquenched with a saturated aq. NaHCO3 solution
  3. extractionextracted with CH2Cl2)
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. customevaporated under reduced pressure
  6. customThe crude product was purified by silica gel column chromatography
  7. washeluting with EtOAc

Sources & evidence

ORD record
ord-1739ddf7c02941cd999f968a7a22aa82
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

Loading…