Sodium Hydroxide → 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoic acid

HRID 1398566Notes

Reaction equation

HRID 1398566 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([OH:26])([CH3:25])[C:20]([O:22]CC)=[O:21])[CH:15]=3)[C:10]([CH3:27])=[N:9]2)[CH:5]=[CH:4][N:3]=1.[OH-].[Na+]>CO>[NH2:1][C:2]1[N:7]=[C:6]([N:8]2[C:16]3[C:11](=[CH:12][CH:13]=[C:14]([C:17]#[C:18][C:19]([OH:26])([CH3:25])[C:20]([OH:22])=[O:21])[CH:15]=3)[C:10]([CH3:27])=[N:9]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68181861ethyl 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoate

Product 1

HCID 681819404-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoic acid

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of ethyl 4-[1-(2-aminopyrimidin-4-yl)-3-methyl-1H-indazol-6-yl]-2-hydroxy-2-methylbut-3-ynoate (120 mg, 0.33 mmol) in methanol (0.5 mL) was introduced sodium hydroxide (0.16 mL of a 2M aqueous solution, 0.33 mmol). After 15 hr at RT, the reaction mixture was concentrated in vacuo and the pH of the aqueous residue adjusted to 7 with 0.5M aqueous hydrochloric acid. The solution was extracted with 3:1 chloroform/isopropanol (5×5 mL extractions) and the combined organic extracts dried (Na2SO4), filtered and concentrated in vacuo to furnish the crude title compound as a yellow solid: 1H NMR (250 MHz, DMSO) delta 1.68 (3H, s), 2.59 (3H, s), 7.07-7.29 (3H, m), 7.37 (2H, dd, J=8.4, 1.2 Hz), 7.87 (1H, d, J=7.7 Hz), 8.28 (1H, d, J=5.9 Hz), 8.85 (1H, s); LC-MS: m/z=+338.00 (M+H)+. This compound, with LC-MS purity=100% UV, was used in the next step without further purification.

Workup

  1. concentrationthe reaction mixture was concentrated in vacuo
  2. extractionThe solution was extracted with 3:1 chloroform/isopropanol (5×5 mL extractions)
  3. dry with materialthe combined organic extracts dried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0d6cabbcc3744f20b4d631b104a061e2
Source dataset
uspto-grants-2014_12
Patent number
US08901313B2

Reaction notes

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