Sodium Hydroxide → HCID 67442608, compound

HRID 1400892Notes

Reaction equation

HRID 1400892 reaction equation
[CH:1]1([NH:4][C:5](=[O:38])[NH:6][C:7]2[CH:36]=[CH:35][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH2:26][CH2:25][N:24]([C:27](=[O:34])[CH2:28][CH2:29][C:30]([O:32]C)=[O:31])[CH2:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:37])[CH:8]=2)[CH2:3][CH2:2]1.[OH-].[Na+]>C1COCC1.CO>[CH:1]1([NH:4][C:5](=[O:38])[NH:6][C:7]2[CH:36]=[CH:35][C:10]([O:11][C:12]3[CH:17]=[CH:16][N:15]=[C:14]4[CH:18]=[C:19]([C:21]5[CH2:26][CH2:25][N:24]([C:27](=[O:34])[CH2:28][CH2:29][C:30]([OH:32])=[O:31])[CH2:23][CH:22]=5)[S:20][C:13]=34)=[C:9]([F:37])[CH:8]=2)[CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 67444143HCID 67444143, compound

Product 1

HCID 67442608HCID 67442608, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a stirred suspension of 272 (120 mg, 0.223 mmol) in THF/MeOH (5/5 mL) was added NaOH 1M (3 mL, 3.00 mmol). The reaction mixture was stirred at RT for 16 h and concentrated. The residue was then diluted with water and extracted with DCM/MeOH. The organic layer was successively washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 15/85 over 20 CV) to afford a material that upon trituration with AcOEt afforded the title compound 273 (10 mg, 0.019 mmol, 9% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): 8.90-8.79 (bs, 1H), 8.35 (d, =5.6 Hz, 1H), 7.64-7.56 (m, 1H), 7.32-7.29 (m, 1H), 7.27-6.96″(m, 4H), 6.68-6.60 (m, 1H), 6.48-6.40 (m, 1H), 5.14-5.01 (m, 1H), 3.94-3.88 (m, 1H), 3.68-3.48 (m, 2H), 2.63-2.56 (m, 2H), 2.50-2.30 (m, 3H), 2.20-2.08 (m, 1H), 1.92-1.79 (m, 1H), 0.57-0.52 (m, 2H), 0.34-0.30 (m, 2H). MS (m/z): 525.39 (M+H).

Workup

  1. concentrationconcentrated
  2. additionThe residue was then diluted with water
  3. extractionextracted with DCM/MeOH
  4. washThe organic layer was successively washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by Biotage (SNAP 25 g cartridge; MeOH/DCM: 0/100 to 15/85 over 20 CV)
  9. customto afford a material that upon trituration with AcOEt

Sources & evidence

ORD record
ord-5cc2a60ef5b84f7cb6c49c9cc16b5102
Source dataset
uspto-grants-2014_12
Patent number
US08906852B2

Reaction notes

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