Trifluoroacetic acid → 4-(4-chlorophenyl)-3-methyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-one

HRID 873796Notes

Reaction equation

HRID 873796 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:11](=[N:12][N:13](CC4C=CC(OC)=CC=4)[C:14]=3[CH3:16])[C:10](=[O:26])[N:9]2[C:27]2[CH:32]=[CH:31][C:30](=[O:33])[N:29]([CH3:34])[CH:28]=2)=[CH:4][CH:3]=1.C(O)(C(F)(F)F)=O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[C:15]3[C:11](=[N:12][NH:13][C:14]=3[CH3:16])[C:10](=[O:26])[N:9]2[C:27]2[CH:32]=[CH:31][C:30](=[O:33])[N:29]([CH3:34])[CH:28]=2)=[CH:4][CH:3]=1

Participants

3

Reactant 2

HCID 6422Trifluoroacetic acidHCID 918262984-(4-Chlorophenyl)-5-(1,6-dihydro-1-methyl-6-oxo-3-pyridinyl)-4,5-dihydro-2-[(4-methoxyphenyl)methyl]-3-methylpyrrolo[3,4-c]pyrazol-6(2H)-one

Product 1

HCID 1177026284-(4-chlorophenyl)-3-methyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo-[3,4-c]pyrazol-6(2H)-oneYield 50.3%

Conditions

Temperature
100 °C

Procedure

In a 2-5 mL MW flask was introduced 4-(4-chlorophenyl)-2-(4-methoxybenzyl)-3-methyl-5-(1-methyl-6-oxo-1,6-dihydropyridin-3-yl)-4,5-dihydropyrrolo[3,4-c]pyrazol-6(2H)-one (Example 1) (85 mg, 0.179 mmol) and TFA (1379 μL, 17.90 mmol). The reaction mixture was stirred for 30 min at 100° C. under MW irradiation, quenched with a saturated aq. NaHCO3 solution, and extracted with CH2Cl2. The combined organic layers were washed with a saturated aq. solution of NaHCO3, dried over Na2SO4, and evaporated. The crude material was purified by silica gel column chromatography (CH2Cl2/MeOH 1-8%) to afford the title compound (32 mg, 0.090 mmol, 50% yield) as a white solid. tR: 3.13 min (HPLC 1); tR: 0.69 min (LC-MS 2); ESI-MS: 355 [M+H]+ (LC-MS 2); Rf=0.40 (CH2Cl2/MeOH 9:1); 1H NMR (400 MHz, DMSO-d6) δ ppm 2.03 (s, 3H) 3.34 (s, 3H) 6.09 (s, 1H) 6.30 (d, J=9.4 Hz, 1H) 7.22 (d, J=8.2 Hz, 2H) 7.35 (d, J=8.6 Hz, 2H) 7.44 (dd, J=9.8, 2.74 Hz, 1H) 7.88 (d, J=3.1 Hz, 1H) 13.35 (br. s., 1H).

Workup

  1. customquenched with a saturated aq. NaHCO3 solution
  2. extractionextracted with CH2Cl2
  3. washThe combined organic layers were washed with a saturated aq. solution of NaHCO3
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe crude material was purified by silica gel column chromatography (CH2Cl2/MeOH 1-8%)

Sources & evidence

ORD record
ord-a9bcfb41d56a4aee9f9f552796e2bd70
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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