Lithium hydroxide, monohydrate → HCID 71259247, compound

HRID 1630316Notes

Reaction equation

HRID 1630316 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:46])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:34](=[O:45])[NH:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH3:44])[CH:38]=3)[C:32]=2[Cl:33])[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].O.[OH-].[Li+]>C(O)C.O>[C:1]([O:5][C@@H:6]([C:12]1[C:13]([CH3:46])=[N:14][C:15]2[N:16]([N:30]=[C:31]([C:34](=[O:45])[NH:35][CH2:36][C:37]3[CH:42]=[CH:41][C:40]([F:43])=[C:39]([CH3:44])[CH:38]=3)[C:32]=2[Cl:33])[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

5

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 71267858HCID 71267858, compound

Product 1

HCID 71259247HCID 71259247, compound

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (2S)-ethyl 2-(tert-butoxy)-2-(3-chloro-2-((4-fluoro-3-methylbenzyl)carbamoyl)-7-(8-fluoro-5-methylchroman-6-yl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)acetate (22 mg, 0.034 mol, 1 equiv) in ethanol (0.45 mL) and water (0.22 mL) was added lithium hydroxide monohydrate (7 mg, 0.168 mmol, 5 equiv). The reaction was heated in an oil bath at 60° C. for 16 h. After cooling to ambient temperature, the reaction was filtered and loaded directly onto reverse phase HPLC (acetonitrile/TFA eluent). The desired compound was isolated as an off white solid (2.4 mg, 11% yield). 1H NMR (500 MHz, CDCl3) δ 7.19-7.15 (m, 2H), 7.14-7.10 (m, 1H), 7.00-6.94 (m, 1H), 6.86 (d, J=10.6 Hz, 1H), 5.08 (s, 1H), 4.57 (d, J=6.3 Hz, 2H), 4.36-4.32 (m, 2H), 2.81 (s, 3H), 2.77-2.72 (m, 2H), 2.27 (d, J=1.7 Hz, 3H), 2.20-2.14 (m, 2H), 1.88 (s, 3H), 1.22 (s, 9H); 19F NMR (471 MHz, CDCl3) δ 119.29 (s, 1F), −139.22 (s, 1F); LCMS (ESI, M+1): 627.5.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. filtrationthe reaction was filtered

Sources & evidence

ORD record
ord-887dbc26677f455eb4ab5ac81878aae9
Source dataset
uspto-grants-2014_07
Patent number
US08791108B2

Reaction notes

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