Stannous Chloride → Acetic Acid

HRID 890536Notes

Reaction equation

HRID 890536 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[CH2:7][NH:6][CH2:5]2.[N:11]([O-])=[O:12].[Na+].Cl[Sn]Cl.O[C:19]1[C:20](=[O:38])[N:21]([C:31]2[CH:36]=[CH:35][C:34]([I:37])=[CH:33][CH:32]=2)[CH2:22][CH2:23][C:24]=1[C:25](=[O:30])[C:26]([F:29])([F:28])[F:27]>Cl.O.CO.CC(O)=O>[I:37][C:34]1[CH:35]=[CH:36][CH:31]=[CH:32][CH:33]=1.[CH2:7]1[C:8]2[C:4](=[CH:3][C:2]([N:1]3[C:19]4[C:20](=[O:38])[N:21]([CH3:31])[CH2:22][CH2:23][C:24]=4[C:25]([C:26]([F:29])([F:28])[F:27])=[N:11]3)=[CH:10][CH:9]=2)[CH2:5][NH:6]1.[CH3:26][C:25]([OH:30])=[O:12]

Participants

10

Reactant 4

HCID 24479Stannous ChlorideHCID 147958622,3-Dihydro-1H-isoindol-5-amineHCID 219368343-hydroxy-1-(4-iodophenyl)-4-(2,2,2-trifluoroacetyl)-5,6-dihydro-1H-pyridin-2-oneHCID 23668193Sodium Nitrite

Product 2

HCID 176Acetic AcidYield 1,599.5%HCID 865899351-(2,3-dihydro-1H-isoindol-5-yl)-6-methyl-3-(trifluoromethyl)-4,5-dihydropyrazolo[5,4-c]pyridin-7-one;iodobenzene

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 313Hydrochloric AcidSolvent2×HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

Part C. The 5-aminoisoindoline (700 mg, 4.11 mmol) made above was dissolved in 6 M HCl (4.6 mL) at rt, then cooled to 0° C. A solution of NaNO2 (340 mg, 4.93 mmol) in water (0.8 mL) was added dropwise, maintaining the reaction temperature below 5° C. After 40 min, AcOH (1.4 mL) was added to the mixture, followed by the dropwise addition of SnCl2 (1.79 g, 9.44 mmol) in concentrated HCl (2.7 mL) at 0° C. The mixture was warmed to 10° C. and stirred for 2 h, then a solution of 3-hydroxy-1-(4-iodophenyl)-4-(2,2,2-trifluoroacetyl)-5,6-dihydro-1H-pyridin-2-one (1.78 g, 4.31 mmol) in MeOH (16 mL) was added and the reaction mixture was heated at 50° C. for 16 h. Methyl alcohol was removed under vacuum and the solid was collected by filtration to give 1-(2,3-dihydro-1H-isoindol-5-yl)-6-methyl-3-trifluoromethyl-1,4,5,6-tetrahydro-pyrazolo[3,4-c]pyridin-7-one; compound with iodo-benzene as an AcOH salt (2.07 g, 86% yield): 1H NMR (500 MHz, DMSO-d6) δ 9.82 (s, br, 2H), 7.75 (d, 2H), 7.66–7.62 (m, 2H), 7.51 (d, 1H), 7.19 (d, 2H), 4.56 (m, 4H), 4.11 (t, 2H), 3.12 (t, 2H); ESI MS m/z 585 (M+H)+.

Workup

  1. temperaturemaintaining the reaction temperature below 5° C
  2. temperatureThe mixture was warmed to 10° C.
  3. temperaturethe reaction mixture was heated at 50° C. for 16 h
  4. customMethyl alcohol was removed under vacuum
  5. filtrationthe solid was collected by filtration

Sources & evidence

ORD record
ord-babf9f960c4b4beaa1fc42e167ce3a32
Source dataset
uspto-grants-2006_02
Patent number
US06995172B2

Reaction notes

Loading…