Hydrochloric Acid → HCID 89462656, compound

HRID 1473279Notes

Reaction equation

HRID 1473279 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]3[CH:29]=[N:28][N:27]([CH2:30][C:31]4[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=4)[C:11]=3[C:12](=[O:26])[N:13]([CH3:25])[C:14]=2[CH:15]([O:18]C2CCCCO2)[C:16]#N)[CH:5]=[CH:6][C:7]=1[CH3:8].[OH-:39].[Na+].[OH2:41].Cl.[Si](C=[N+]=[N-])(C)(C)[CH3:44]>O.C(O)(=O)C.CCO>[CH3:1][C:2]1[CH:3]=[C:4]([C:9]2[C:10]3[CH:29]=[N:28][N:27]([CH2:30][C:31]4[CH:32]=[CH:33][C:34]([O:37][CH3:38])=[CH:35][CH:36]=4)[C:11]=3[C:12](=[O:26])[N:13]([CH3:25])[C:14]=2[CH:15]([OH:18])[C:16]([O:41][CH3:44])=[O:39])[CH:5]=[CH:6][C:7]=1[CH3:8]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 167693TrimethylsilyldiazomethaneHCID 23719242Sodium hydroxide--water (1/1/1)HCID 89462943HCID 89462943, compound

Product 1

HCID 89462656HCID 89462656, compoundYield 72.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
140 °C

Procedure

A mixture of 2-(4-(3,4-dimethyl phenyl)-1-(4-methoxybenzyl)-6-methyl-7-oxo-6,7-dihydro-1H-pyrazolo[3,4-c]pyridin-5-yl)-2-((tetrahydro-2H-pyran-2-yl)oxy)acetonitrile 267 mg, 0.52 mmol), 20% sodium hydroxide/water (5.0 g, 25 mmol) and EtOH (5 mL) was heated in a sealed tube at 140° C. for 18 h. The mixture was acidified to pH 3 with 1 M hydrochloric acid, diluted with water and extracted with EtOAc. The organic phase was dried over sodium sulfate and concentrated. The residue was dissolved in MeOH (10 mL) and PTS (80 mg, 0.421 mmol) was added. After 1 h at ambient temperature the mixture was treated with TMS-diazomethane (3 mL, 6 mmol, 2M/hexanes) and stirring continued for 1.5 h. Acetic acid was added until bubbling stopped and the mixture was concentrated and purified on silica using EtOAc/hexanes 0-50% to provide the title compound (175 mg, 72%). 1H NMR (400 MHz, CDCl3) δ ppm 7.4-7.5 (m, 3H), 7.1-7.3 (m, 3H), 6.85 (d, 2H), 5.95 (s, 2H), 5.35 (d, 1H), 3.79 (s, 3H), 3.78 (s, 3H), 3.6 (s, 3H), 2.33 (s, 3H), 2.32 (s, 3H); ES-LCMS: 462.22 (M+1).

Workup

  1. extractionextracted with EtOAc
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated
  4. dissolutionThe residue was dissolved in MeOH (10 mL)
  5. additionPTS (80 mg, 0.421 mmol) was added
  6. customuntil bubbling
  7. concentrationthe mixture was concentrated
  8. custompurified on silica

Sources & evidence

ORD record
ord-6d74f84e68804ceb8cd2c198e1e7224e
Source dataset
uspto-grants-2015_04
Patent number
US09012642B2

Reaction notes

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