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

HRID 472878Notes

Reaction equation

HRID 472878 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:42])=[N:13][C:14]2[N:15]([N:29]=[C:30]([C:32]3[CH:41]=[CH:40][C:39]4[CH2:38][CH2:37][CH2:36][CH2:35][C:34]=4[CH:33]=3)[CH:31]=2)[C:16]=1[C:17]1[C:18]([CH3:28])=[C:19]2[C:24](=[C:25]([F:27])[CH:26]=1)[O:23][CH2:22][CH2:21][CH2:20]2)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>CO>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:42])=[N:13][C:14]2[N:15]([N:29]=[C:30]([C:32]3[CH:41]=[CH:40][C:39]4[CH2:38][CH2:37][CH2:36][CH2:35][C:34]=4[CH:33]=3)[CH:31]=2)[C:16]=1[C:17]1[C:18]([CH3:28])=[C:19]2[C:24](=[C:25]([F:27])[CH:26]=1)[O:23][CH2:22][CH2:21][CH2:20]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 66692989HCID 66692989, compound

Product 1

HCID 66693153(2S)-2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acidYield 53.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (22 mg, 0.038 mmol) and 1M NaOH (0.154 mL, 0.154 mmol) in MeOH (2 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)-5-methyl-2-(5,6,7,8-tetrahydronaphthalen-2-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid (12 mg, 0.020 mmol, 53.1% yield) as white solid. 1H NMR (500 MHz, CDCl3) δ: 7.56 (d, J=7.9 Hz, 1H), 7.52 (s, 1H), 7.09 (d, J=7.9 Hz, 1H), 6.96 (d, J=10.7 Hz, 1H), 6.86 (s, 1H), 5.11 (s, 1H), 4.39-4.31 (m, 2H), 2.86-2.75 (m, 6H), 2.73 (s, 3H), 2.20-2.18 (m, 2H), 1.95 (s, 3H), 1.84-1.80 (m, 4H), 1.24 (s, 9H). LCMS (M+H)=558.4.

Workup

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

Sources & evidence

ORD record
ord-a67d187a2691495d9732a5cf139aa36c
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

Loading…