Sodium Hydroxide → (2S)-2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid

HRID 1468750Notes

Reaction equation

HRID 1468750 reaction equation
[NH2:1][C:2]1[CH:34]=[C:5]2[N:6]=[C:7]([CH3:33])[C:8]([C@H:22]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C:23]([O:25]CC)=[O:24])=[C:9]([C:10]3[C:11]([CH3:21])=[C:12]4[C:17](=[C:18]([F:20])[CH:19]=3)[O:16][CH2:15][CH2:14][CH2:13]4)[N:4]2[N:3]=1.[OH-].[Na+]>CCO>[NH2:1][C:2]1[CH:34]=[C:5]2[N:6]=[C:7]([CH3:33])[C:8]([C@H:22]([O:28][C:29]([CH3:30])([CH3:31])[CH3:32])[C:23]([OH:25])=[O:24])=[C:9]([C:10]3[C:11]([CH3:21])=[C:12]4[C:17](=[C:18]([F:20])[CH:19]=3)[O:16][CH2:15][CH2:14][CH2:13]4)[N:4]2[N:3]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86695370(2S)-ethyl 2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate

Product 1

HCID 71730302(2S)-2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acidYield 85%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of (2S)-ethyl 2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetate (1.20 g, 2.55 mmol), 1N NaOH (3.83 mL, 3.83 mmol) in EtOH (20 mL) was stirred at rt for 16 h. LCMS indicated a small amount of starting material remaining, therefore, the reaction mixture washeated at 60° C. for 2 h. At this time, LCMS indicated that the ester hydrolysis was complete. The reaction mixture was then concentrated in vacuo, and the residue was adjusted to pH=4 using 1N HCl. A white precipitate formed and was collected by filtration, washed with water, and dried in vacuo to obtain (2S)-2-(2-amino-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-(tert-butoxy)acetic acid (1.06 g, 2.16 mmol, 85% yield) as a off-white solid. 1H NMR (500 MHz, CDCl3) δ 6.90 (d, J=10.56 Hz, 1H), 5.91 (s, 1H), 4.97 (s, 1H), 4.26-4.35 (m, 2H), 2.74 (m, 2H), 2.65 (s, 3H), 2.11-2.18 (m, 2H), 1.95 (s, 3H), 1.21 (s, 9H). LCMS (M+H)=443.23.

Workup

  1. waitthe reaction mixture washeated at 60° C. for 2 h
  2. concentrationThe reaction mixture was then concentrated in vacuo
  3. customA white precipitate formed
  4. filtrationwas collected by filtration
  5. washwashed with water
  6. customdried in vacuo

Sources & evidence

ORD record
ord-f13c593b5ca44078bd4fdf1e7bb4a32b
Source dataset
uspto-grants-2015_04
Patent number
US09006235B2

Reaction notes

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