Acetic Acid → (2S)-2-(tert-Butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(2'-methyl-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acid

HRID 472838Notes

Reaction equation

HRID 472838 reaction equation
[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:45])=[N:13][C:14]2[N:15]([N:29]=[C:30]([C:32]3[CH:33]=[C:34]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[CH3:44])[CH:35]=[CH:36][CH:37]=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+].C(O)(=O)C>O1CCOCC1.O>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([CH3:45])=[N:13][C:14]2[N:15]([N:29]=[C:30]([C:32]3[CH:33]=[C:34]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][C:39]=4[CH3:44])[CH:35]=[CH:36][CH:37]=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

6

Reactant 3

HCID 176Acetic AcidHCID 14798Sodium HydroxideHCID 66693089(2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(2'-methyl-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate

Product 1

HCID 66695859(2S)-2-(tert-Butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(2'-methyl-[1,1'-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetic acidYield 67.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-5-methyl-2-(2′-methyl-[1,1′-biphenyl]-3-yl)pyrazolo[1,5-a]pyrimidin-6-yl)acetate (1.28 g, 2.1 mmol) in dioxane (12 mL) was added 1 N NaOH aqueous solution (9 mL, 9 mmol). The reaction mixture was stirred at 50° C. for 2 h. The reaction mixture was diluted with water (50 ml) and neutralized with acetic acid. The resulted mixture was extracted with ethyl acetate (3×100 ml). The organic phase was combined and dried by sodium sulfate. The solvents were evaporated and the crude product was purified by preparative HPLC to afford (840 mg, 66%) of the title compound. Preparative HPLC condition: Waters Sunfire OBD C18 30×100 mm 5 u, 15 to 60% B over 18 minute gradient, 2 minute hold time, A=5% acetonitrile 95% water 10 mM Ammonium Acetate, B=95% acetonitrile 5% water 10 mM Ammonium Acetate. Flow rate: 40 ml/min. 1H NMR (400 MHz, DMSO-d6) δ 7.86-7.75 (m, 2H), 7.50 (t, J=7.7 Hz, 1H), 7.40-7.22 (m, 5H), 7.18 (s, 1H), 7.09 (d, J=11.0 Hz, 1H), 4.83 (s, 1H), 4.34-4.22 (m, 2H), 2.82-2.66 (m, 5H), 2.24 (s, 3H), 2.13-2.02 (m, 2H), 1.83 (s, 3H), 1.09 (s, 9H).

Workup

  1. extractionThe resulted mixture was extracted with ethyl acetate (3×100 ml)
  2. dry with materialdried by sodium sulfate
  3. customThe solvents were evaporated
  4. customthe crude product was purified by preparative HPLC

Sources & evidence

ORD record
ord-44a4dbd912484548a372b20dc6968ef7
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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