Sodium Hydroxide → HCID 86679694, compound

HRID 1507117Notes

Reaction equation

HRID 1507117 reaction equation
[OH-:1].[Na+].[CH:3]([C:5]1[C:13]2[C:8](=[CH:9][CH:10]=[C:11]([C:14]3[CH:15]=[C:16]([NH:20][C:21](=[O:25])[N:22]([CH3:24])[CH3:23])[CH:17]=[N:18][CH:19]=3)[CH:12]=2)[N:7]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[N:6]=1)=[O:4]>O.O1CCOCC1.[N+]([O-])([O-])=O.[Ag+]>[CH3:23][N:22]([CH3:24])[C:21](=[O:25])[NH:20][C:16]1[CH:15]=[C:14]([C:11]2[CH:12]=[C:13]3[C:8](=[CH:9][CH:10]=2)[N:7]([CH:26]2[CH2:31][CH2:30][CH2:29][CH2:28][O:27]2)[N:6]=[C:5]3[C:3]([OH:1])=[O:4])[CH:19]=[N:18][CH:17]=1

Participants

6

Reactant 2

HCID 14798Sodium HydroxideHCID 86679695HCID 86679695, compound

Product 1

HCID 86679694HCID 86679694, compoundYield 70%

Reagents, catalysts & solvents 3

HCID 24470Silver NitrateCatalystHCID 962WaterSolvent3×HCID 312751,4-DioxaneSolvent

Procedure

A solution of sodium hydroxide (0.173 g, 4.33 mmol) in water (5 mL) was added to a solution of silver nitrate (0.367 g, 2.16 mmol) in water (5 mL) to give a brown precipitate. 3-(5-(3-formyl-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)pyridin-3-yl)-1,1-dimethylurea (CXXIII) (0.340 g, 0.86 mmol) was dissolved in 1,4-dioxane (10 mL) and added to the reaction which was stirred overnight at room temperature. The solution was diluted with water and then extracted with diethyl ether. The aqueous layer was separated and carefully brought to pH=3 with aqueous HCl. The aqueous layer was then extracted with 10% iPrOH/chloroform. The combined organic layers were then dried (Na2SO4), filtered and concentrated to give 5-(5-(3,3-dimethylureido)pyridin-3-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole-3-carboxylic acid (CXXIV) as a brownish white solid (246 mg, 0.60 mmol, 70% yield). 1H NMR (DMSO-d6) δ ppm 13.26 (br. s, 1H), 8.87 (s, 1H), 8.63 (s, 1H), 8.41 (s, 1H), 8.34 (s, 1H), 8.03 (d, J=7.1 Hz, 1H), 7.86 (dd, J=7.2, 1.3 Hz, 1H), 6.06 (dd, J=8.0, 4.0 Hz, 1H), 3.92 (m, 1H), 3.80 (m, 1H), 2.98 (s, 6H), 2.42-2.39 (m, 1H), 2.03-2.02 (m, 2H), 1.79-1.77 (m, 1H) 1.61 (m, 2H); ESIMS found for C21H23N5O4 m/z 410.0 (M+H).

Workup

  1. customto give a brown precipitate
  2. additionadded to the reaction which
  3. extractionextracted with diethyl ether
  4. customThe aqueous layer was separated
  5. extractionThe aqueous layer was then extracted with 10% iPrOH/chloroform
  6. dry with materialThe combined organic layers were then dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-b1e57bc7fb444c10af04e126b8867b12
Source dataset
uspto-grants-2015_12
Patent number
US09221793B2

Reaction notes

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