Sulfamic Acid → 4-(4-chlorophenyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-ethyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one

HRID 873912Notes

Reaction equation

HRID 873912 reaction equation
Cl.[NH:2]([C:4]1[C:5]([O:12][CH3:13])=[N:6][C:7]([O:10][CH3:11])=[N:8][CH:9]=1)[NH2:3].CC([O-])=O.[Na+].S(=O)(=O)(O)N.[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]2[N:35]([C:36]3[CH:41]=[C:40]([CH3:42])[C:39](=[O:43])[N:38]([CH3:44])[CH:37]=3)[C:34](=[O:45])[C:33](=O)[CH:32]2[C:47](=O)[CH2:48][CH3:49])=[CH:27][CH:26]=1.C([O-])(O)=O.[Na+]>CO>[Cl:24][C:25]1[CH:30]=[CH:29][C:28]([CH:31]2[C:32]3[C:47]([CH2:48][CH3:49])=[N:3][N:2]([C:4]4[C:5]([O:12][CH3:13])=[N:6][C:7]([O:10][CH3:11])=[N:8][CH:9]=4)[C:33]=3[C:34](=[O:45])[N:35]2[C:36]2[CH:41]=[C:40]([CH3:42])[C:39](=[O:43])[N:38]([CH3:44])[CH:37]=2)=[CH:27][CH:26]=1

Participants

7

Reactant 5

HCID 5987Sulfamic AcidHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 1177027665-(4-Chlorophenyl)-1-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4-propionylpyrrolidine-2,3-dioneHCID 1177027745-Hydrazinyl-2,4-dimethoxypyrimidine hydrochloride

Product 1

HCID 862920014-(4-chlorophenyl)-1-(2,4-dimethoxypyrimidin-5-yl)-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-3-ethyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-oneYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 5-hydrazinyl-2,4-dimethoxypyrimidine hydrochloride (Step 46.8) (413 mg, 2 mmol) in MeOH (5 mL) were added NaOAc (123 mg, 1.5 mmol), sulfamic acid (99 mg, 1 mmol) and 5-(4-chlorophenyl)-1-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-4-propionylpyrrolidine-2,3-dione (Step 60.1) (204 mg, 0.5 mmol) and the reaction mixture was stirred for 2.5 hr at 100° C. in the MW. The reaction mixture was added to a saturated aq. NaHCO3 solution and the aq. layer was extracted with EtOAc. Combined extracts were washed with brine, dried over MgSO4, filtered and concentrated under reduced pressure. The crude material was purified by silica gel column chromatography (hexane/EtOAc/MeOH 80:20:2 to 0:10:1) followed by preparative HPLC to afford, after crystallization from THF/Et2O, the title product (68 mg, 0.124 mmol, 25% yield) as a solid. tR: 1.03 min (LC-MS 2); ESI-MS: 521 [M+H]+ (LC-MS 2); Rf=0.36 (EtOAc/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 0.95 (t, J=7.8 Hz, 3H) 1.92 (s, 3H) 2.36 (m, 1H) 2.44 (m, 1H) 3.33 (s, 3H) 3.96 (s, 3H) 3.99 (s, 3H) 6.24 (m, 1H) 7.34 (m, 2H) 7.37-7.45 (m, 3H) 7.72 (s, 1H) 8.59 (s, 1H).

Workup

  1. extractionthe aq. layer was extracted with EtOAc
  2. washCombined extracts were washed with brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc/MeOH 80:20:2 to 0:10:1)
  7. customto afford
  8. customafter crystallization from THF/Et2O

Sources & evidence

ORD record
ord-636e169cb8f54d9d96ae1deceece96cb
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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