Sodium Hydroxide → HCID 68194835, compound

HRID 2169653Notes

Reaction equation

HRID 2169653 reaction equation
C([O:4][C:5]([CH3:33])([CH2:7][CH2:8][CH2:9][N:10]1[CH2:19][C@@H:18]2[CH2:20][O:21][CH2:22][CH2:23][N:17]2[C:16]2[N:15]=[C:14]([C:24]3[CH:32]=[CH:31][CH:30]=[C:29]4[C:25]=3[CH:26]=[CH:27][NH:28]4)[N:13]=[CH:12][C:11]1=2)[CH3:6])(=O)C.[OH-].[Na+]>CO>[NH:28]1[C:29]2[C:25](=[C:24]([C:14]3[N:13]=[CH:12][C:11]4[N:10]([CH2:9][CH2:8][CH2:7][C:5]([CH3:33])([OH:4])[CH3:6])[CH2:19][C@@H:18]5[CH2:20][O:21][CH2:22][CH2:23][N:17]5[C:16]=4[N:15]=3)[CH:32]=[CH:31][CH:30]=2)[CH:26]=[CH:27]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 68195323HCID 68195323, compound

Product 1

HCID 68194835HCID 68194835, compoundYield 71.1%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
50 °C

Procedure

To a 25 mL pear flask was added (R)-5-(2-(1H-indol-4-yl)-6a,7,9,10-tetrahydro-[1,4]oxazino[3,4-h]pteridin-5(6H)-yl)-2-methylpentan-2-yl acetate (PREPARATION x82, 48 mg, 0.107 mmol) in methanol (3 mL) to give a yellow solution. Aqueous NaOH (3N, 0.4 mL) was added and the mixture was stirred at 50° C. for 4 hours, before being cooled to room temperature. The reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate, and the aqueous layer was extracted a second time with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and concentrated. After trituration with Et2O, the solid product was dried in vacuo to give the title compound as an off-white solid (31 mg, 71%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.10 (s, 6H), 1.32-1.48 (m, 2 H), 1.53-1.73 (m, 2 H), 2.95-3.10 (m, 2 H), 3.11-3.25 (m, 2 H), 3.26-3.40 (m, 2H), 3.50-3.64 (m, 2 H), 3.93 (dd, J=10.99, 3.16 Hz, 1 H), 4.06 (dd, J=11.49, 3.16 Hz, 1 H), 4.19 (s, 1 H), 4.52 (d, J=11.62 Hz, 1 H), 7.11 (t, J=7.71 Hz, 1 H), 7.29-7.44 (m, 3 H), 7.77 (s, 1 H), 7.93 (dd, J=7.45, 0.88 Hz, 1 H), 11.11 (br s, 1 H); ESI-MS m/z [M+H]+ calc'd for C23H29N5O2, 408.24; found 408.3.

Workup

  1. customto give a yellow solution
  2. temperaturebefore being cooled to room temperature
  3. customThe reaction mixture was partitioned between saturated NaHCO3 and ethyl acetate
  4. extractionthe aqueous layer was extracted a second time with ethyl acetate
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dry with materialAfter trituration with Et2O, the solid product was dried in vacuo

Sources & evidence

ORD record
ord-e92b28b3f8764a30ae3db56ead1ca53d
Source dataset
uspto-grants-2015_06
Patent number
US09045496B2

Reaction notes

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