Acetic Anhydride → HCID 91826327, compound

HRID 873984Notes

Reaction equation

HRID 873984 reaction equation
[NH2:1][C:2]1[C:3]2[N:4]([C:28]([CH3:31])=[N:29][N:30]=2)[N:5]=[C:6]([N:8]2[CH:15]([C:16]3[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=3)[C:14]3[C:13]([CH3:23])=[N:12][N:11]([CH:24]4[CH2:26][CH2:25]4)[C:10]=3[C:9]2=[O:27])[CH:7]=1.[CH3:32][C:33](OC(C)=O)=[O:34]>N1C=CC=CC=1>[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([CH:15]2[C:14]3[C:13]([CH3:23])=[N:12][N:11]([CH:24]4[CH2:26][CH2:25]4)[C:10]=3[C:9](=[O:27])[N:8]2[C:6]2[CH:7]=[C:2]([NH:1][C:33](=[O:34])[CH3:32])[C:3]3[N:4]([C:28]([CH3:31])=[N:29][N:30]=3)[N:5]=2)=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 117702652HCID 117702652, compound

Product 1

HCID 91826327HCID 91826327, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Conditions

Temperature
115 °C

Procedure

A flask was charged with 5-(8-amino-3-methyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4,5-dihydropyrrolo[3,4-c]pyrazol-6(1H)-one (Step 126.3) (40 mg, 0.092 mmol) and Ac2O (0.434 mL, 4.60 mmol) in pyridine (2 mL) under Ar and the resulting mixture was heated up and stirred for 20 hr at 115° C. The reaction was quenched with a saturated aq.NaHCO3 solution and extracted with EtOAc. The combined organic layers were washed with a saturated aq. NaHCO3 solution, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 1-4%) and triturated in Et2O to afford the title product (27 mg, 0.057 mmol, 62% yield) as white solid. tR: 4.73 min (HPLC 1); tR: 1.07 min (LC-MS 2); ESI-MS: 477 [M+H]+ (LC-MS 2); ESI-MS: 475 [M−H]− (LC-MS 2); Rf=0.50 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 1.02-1.11 (m, 2H) 1.17-1.30 (m, 2H) 1.90 (s, 3H) 2.25 (s, 3H) 2.51 (s, 3H) 3.76-3.88 (m, 1H) 6.43 (s, 1H) 7.29-7.37 (m, 2H) 7.38-7.48 (m, 2H) 9.12 (s, 1H) 11.07 (s, 1H).

Workup

  1. temperaturethe resulting mixture was heated up
  2. customThe reaction was quenched with a saturated aq
  3. extractionNaHCO3 solution and extracted with EtOAc
  4. washThe combined organic layers were washed with a saturated aq. NaHCO3 solution
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product was purified by silica gel column chromatography (CH2Cl2/MeOH 1-4%)
  9. customtriturated in Et2O

Sources & evidence

ORD record
ord-38586d0602f74ebf869d3c22a88d1a27
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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