Lithium Hydroxide → HCID 66692613, compound

HRID 472844Notes

Reaction equation

HRID 472844 reaction equation
OC(C(F)(F)F)=O.[C:8]([O:12][C@@H:13]([C:18]1[C:19]([CH3:60])=[N:20][C:21]2[N:22]([N:36]=[C:37]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:38]=2[C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=3)[CH:40]=2)[C:23]=1[C:24]1[C:25]([CH3:35])=[C:26]2[C:31](=[C:32]([F:34])[CH:33]=1)[O:30][CH2:29][CH2:28][CH2:27]2)[C:14]([O:16]C)=[O:15])([CH3:11])([CH3:10])[CH3:9].[Li+].[OH-]>O1CCOCC1>[C:8]([O:12][C@@H:13]([C:18]1[C:19]([CH3:60])=[N:20][C:21]2[N:22]([N:36]=[C:37]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[C:38]=2[C:39]2[CH:44]=[CH:43][CH:42]=[C:41]([O:45][CH2:46][C:47]3[CH:52]=[CH:51][C:50]([F:53])=[CH:49][CH:48]=3)[CH:40]=2)[C:23]=1[C:24]1[C:25]([CH3:35])=[C:26]2[C:31](=[C:32]([F:34])[CH:33]=1)[O:30][CH2:29][CH2:28][CH2:27]2)[C:14]([OH:16])=[O:15])([CH3:11])([CH3:10])[CH3:9]

Participants

4

Reactant 2

HCID 3939Lithium HydroxideHCID 131731148HCID 131731148, compound

Product 1

HCID 66692613HCID 66692613, compoundYield 50.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (2S)-methyl 2-(tert-butoxy)-2-(7-(8-fluoro-5-methylchroman-6-yl)-3-(3-((4-fluorobenzyl)oxy)phenyl)-5-methyl-2-phenylpyrazolo[1,5-a]pyrimidin-6-yl)acetate TFA salt (10 mg, 0.014 mmol) in dioxane (0.5 mL) was added 1.0 N LiOH aqueous solution (0.5 mL, 0.5 mmol). The reaction mixture was stirred at 60° C. for 48 h. The reaction mixture was filtered and the filtrate was purified by preparative HPLC to afford (5 mg, 50%) of the title compound as the TFA salt. Preparative HPLC condition: Phenomenex Luna C18 30×100 mm S10, 50 to 100% B over 22 min gradient, 6 min hold time, A=10% methanol 90% water 0.1% TFA, B=90% methanol 10% water 0.1% TFA. Flow rate: 40 mL/min. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.087 (9H, br. s.), 1.88 (2H, br. s.), 2.51 (2H, br. s.), 2.71 (3H, br. s.) 2.82-2.96 (2H, m), 4.29 (2H, br. s.), 4.6 (1H, s), 5.02 (2H, s), 6.9 (1H, s), 7.14-7.47 (12H, m), 7.97 (1H, s).

Workup

  1. filtrationThe reaction mixture was filtered
  2. customthe filtrate was purified by preparative HPLC

Sources & evidence

ORD record
ord-176bf6e00ccc4eda9c420b4e70aaf78d
Source dataset
uspto-grants-2014_01
Patent number
US08633200B2

Reaction notes

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