Iodoethane → 4-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-ethyl-3-methyl-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-one

HRID 873980Notes

Reaction equation

HRID 873980 reaction equation
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:17]3[C:16]([CH3:18])=[N:15][NH:14][C:13]=3[C:12](=[O:19])[N:11]2[C:20]2[CH:21]=[C:22]([CH3:30])[C:23]3[N:24]([C:26]([CH3:29])=[N:27][N:28]=3)[CH:25]=2)=[CH:6][CH:5]=1.I[CH2:32][CH3:33]>CN(C=O)C.CCOCC>[Cl:3][C:4]1[CH:9]=[CH:8][C:7]([CH:10]2[C:17]3[C:13](=[N:14][N:15]([CH2:32][CH3:33])[C:16]=3[CH3:18])[C:12](=[O:19])[N:11]2[C:20]2[CH:21]=[C:22]([CH3:30])[C:23]3[N:24]([C:26]([CH3:29])=[N:27][N:28]=3)[CH:25]=2)=[CH:6][CH:5]=1

Participants

6

Reactant 3

HCID 6340IodoethaneHCID 24758Sodium hydrideHCID 178434164HCID 178434164, compound

Product 1

HCID 862925834-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-ethyl-3-methyl-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-oneYield 18%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

NaH (21.18 mg, 0.529 mmol) was added to a stirred solution of 4-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Example 98) (160 mg, 0.407 mmol) in DMF (4 mL) at 0° C. and the resulting mixture was stirred at 0° C. for 30 min. Iodoethane (0.039 mL, 0.489 mmol) was added and the reaction mixture was stirred at RT for 30 min. The reaction was quenched with water, diluted with EtOAc and both phases were separated. The aq. layer was extracted with EtOAc. The combined organic layers were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The crude material was purified by preparative achiral SFC (column NH2, gradient 19-24% in 6 min, total 11 min) to afford, after trituration in Et2O, 31 mg, 0.074 mmol, 18% yield) as white solid. tR: 0.88 min (LC-MS 2); ESI-MS: 421 [M+H]+ (LC-MS 2); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.38 (t, J=7.2 Hz, 3H) 2.13 (s, 3H) 2.46 (s, 3H) 2.63 (s, 3H) 4.20 (q, J=7.2 Hz, 2H) 6.49 (s, 1H) 7.33-7.40 (m, 5H) 8.46 (s, 1H).

Workup

  1. stirringthe reaction mixture was stirred at RT for 30 min
  2. customThe reaction was quenched with water
  3. additiondiluted with EtOAc
  4. customboth phases were separated
  5. extractionThe aq. layer was extracted with EtOAc
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated under reduced pressure
  9. customThe crude material was purified by preparative achiral SFC (column NH2, gradient 19-24% in 6 min, total 11 min)
  10. customto afford

Sources & evidence

ORD record
ord-731d4506c09947baa456b716179f3e2e
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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