Sodium Hydroxide → HCID 118414945, compound

HRID 1054319Notes

Reaction equation

HRID 1054319 reaction equation
[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][C:8]1[CH:9]=[C:10]([C:32]([O:34]CC)=[O:33])[C:11]2[C:16]([CH3:17])=[N:15][N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:21][CH:20]=3)[C:12]=2[N:13]=1.[OH-].[Na+]>C1COCC1.O>[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][NH:7][C:8]1[CH:9]=[C:10]([C:32]([OH:34])=[O:33])[C:11]2[C:16]([CH3:17])=[N:15][N:14]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([O:25][C:26]4[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=4)=[CH:21][CH:20]=3)[C:12]=2[N:13]=1

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 118414927HCID 118414927, compound

Product 1

HCID 118414945HCID 118414945, compoundYield 61%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

(see, e.g., Neres, J., et al., J Med Chem 2013, 56, 2385-405). A solution of ester 51 (40 mg, 0.08 mmol) and 1N NaOH (3.5 mL, 3.5 mmol) in THF (1.5 mL) was refluxed for 3 h. Reaction mixture was diluted with water (10 mL) and washed with EtOAc (10 mL×2). Aqueous layer was acidified with 1N HCl and extracted with EtOAc (10 mL×2). Combined organic extracts were washed with brine, dried (Na2SO4) and filtered. The solvent was removed under reduced pressure to give the title compound (22 mg, 61%) as an orange solid. 99% pure by HPLC. 1H NMR (500 MHz, DMSO-d6) δ 7.79 (t, J=5.1 Hz, 1H), 7.54 (s, 1H), 7.34 (t, J=7.6 Hz, 2H), 7.27 (d, J=8.1 Hz, 2H), 7.10 (t, J=6.8 Hz, 1H), 6.95 (d, J=7.9 Hz, 2H), 6.90 (d, J=8.3 Hz, 2H), 6.86 (s, 1H), 6.33 (s, 1H), 6.25 (s, 1H), 5.35 (s, 2H), 4.57 (d, J=5.2 Hz, 2H), 2.41 (s, 3H). 13C NMR (125 MHz, DMSO-d6) δ 167.35, 157.85, 157.05, 156.29, 153.26, 152.02, 142.37, 140.38, 135.41, 133.48, 130.46, 130.44, 130.08, 123.85, 118.98, 118.97, 110.81, 107.38, 103.37, 49.09, 37.87, 15.96. ESI MS: m/z 455.0 (M+H)+.

Workup

  1. customReaction mixture
  2. washwashed with EtOAc (10 mL×2)
  3. extractionextracted with EtOAc (10 mL×2)
  4. washCombined organic extracts were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-a020c0fbb2df4fc1a89531745ad22d78
Source dataset
uspto-grants-2016_07
Patent number
US09394303B2

Reaction notes

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