Sodium Methoxide → HCID 54692324, compound

HRID 1162851Notes

Reaction equation

HRID 1162851 reaction equation
C([O:7][C:8]1[C:13](=[O:14])[N:12]([CH:15]([CH3:17])[CH3:16])[C:11](=[O:18])[N:10]2[CH:19]([CH2:32][CH2:33][OH:34])[CH2:20][N:21]([CH2:24][C:25]3[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=3)[C:22](=[O:23])[C:9]=12)(=O)C(C)(C)C.C[O-].[Na+]>CO>[F:31][C:28]1[CH:27]=[CH:26][C:25]([CH2:24][N:21]2[CH2:20][CH:19]([CH2:32][CH2:33][OH:34])[N:10]3[C:11](=[O:18])[N:12]([CH:15]([CH3:17])[CH3:16])[C:13](=[O:14])[C:8]([OH:7])=[C:9]3[C:22]2=[O:23])=[CH:30][CH:29]=1

Participants

4

Reactant 2

HCID 10942334Sodium MethoxideHCID 68431466HCID 68431466, compound

Product 1

HCID 54692324HCID 54692324, compound

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a stirred solution of 2-(4-fluorobenzyl)-4-(2-hydroxyethyl)-7-isopropyl-1,6,8-trioxo-1,3,4,6,7,8-hexahydro-2H-pyrazino[1,2-c]pyrimidine-9-yl pivalate (Example 74, Step 2, 40 mg, 0.08 mmol) in methanol (0.5 mL) was added sodium methoxide (25 wt. % solution in methanol, 1.6 mL) and the mixture stirred at room temperature for 20 min. The reaction was quenched by dropwise addition of 1 N hydrochloric acid and the solvent was removed in vacuo. The resulting residue was taken up in methylene chloride, filtered, and the filtrate concentrated. The residue was purified by reverse phase preparative HPLC (95:5 to 5:95 A:B where A=0.1% TFA-H2O and B=0.1% TFA-MeCN over 30 min) to afford the title compound. 1H NMR (CD3OD, 400 MHz): δ 7.44-7.40 (m, 2 H), 7.13-7.08 (m, 2 H), 5.19-5.15 (m, 1 H), 4.92-4.75 (m, 2 H), 4.51 (d, J=14.4 MHz, 1 H), 3.75 (dd, J=3.8 MHz, 13.4 MHz, 1 H), 3.51 (dd, J=1.6 MHz, 13.6 MHz, 1 H), 3.42-3.30 (m, 2 H), 1.76-1.71 (m, 1 H), 1.62-1.57 (m, 1 H), 1.45 (d, J=7.2 MHz, 6 H). HRMS (FT/ICR) M+H: calcd for (C19H23FN3O5)+ 392.1616. found 392.1625.

Workup

  1. customThe reaction was quenched by dropwise addition of 1 N hydrochloric acid
  2. customthe solvent was removed in vacuo
  3. filtrationfiltered
  4. concentrationthe filtrate concentrated
  5. customThe residue was purified by reverse phase preparative HPLC (95:5 to 5:95 A:B where A=0.1% TFA-H2O and B=0.1% TFA-MeCN over 30 min)

Sources & evidence

ORD record
ord-c9cc40c1deed400982f9a9598dbdd261
Source dataset
uspto-grants-2010_10
Patent number
US07820680B2

Reaction notes

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