Sodium Hydroxide → (2S)-2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 1630312Notes

Reaction equation

HRID 1630312 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:44])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33](=[O:43])[NH:34][CH2:35][C:36]3[CH:41]=[CH:40][C:39]([F:42])=[CH:38][CH:37]=3)[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:44])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:33](=[O:43])[NH:34][CH2:35][C:36]3[CH:37]=[CH:38][C:39]([F:42])=[CH:40][CH:41]=3)[CH:32]=2)[C:17]=1[C:18]1[C:19]([CH3:29])=[C:20]2[C:25](=[C:26]([F:28])[CH:27]=1)[O:24][CH2:23][CH2:22][CH2:21]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 71267848(2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 71259175(2S)-2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acidYield 66.4%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (2S)-ethyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (12 mg, 0.020 mmol) and 1M NaOH (0.079 mL, 0.079 mmol) in MeOH (1 mL) was heated at 60° C. for 16 h. Then, the reaction mixture was cooled and purified by prep HPLC to afford (2S)-2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-2-((4-fluorobenzyl)carbamoyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (8 mg, 0.013 mmol, 66.4% yield) as white solid. 1H NMR (500 MHz, CHLOROFORM-d) δ: 7.31 (dd, J=8.5, 5.5 Hz, 2H), 7.26 (t, J=6.4 Hz, 1H), 7.21 (s, 1H), 7.05-6.99 (m, 2H), 6.87 (d, J=10.7 Hz, 1H), 5.02 (s, 1H), 4.60 (d, J=6.4 Hz, 2H), 4.35-4.32 (m, 2H), 2.77 (s, 3H), 2.76-2.71 (m, 2H), 2.20-2.14 (m, 2H), 1.85 (s, 3H), 1.19 (s, 9H). LCMS (M+H)=579.4.

Workup

  1. temperatureThen, the reaction mixture was cooled
  2. custompurified by prep HPLC

Sources & evidence

ORD record
ord-a237361c90eb4d59beab31d49771b8e1
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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