Hydrochloric Acid → HCID 59472146, compound

HRID 78639Notes

Reaction equation

HRID 78639 reaction equation
[NH2:1][C:2]1[C:3]([C:19]2[O:23][C:22]([C:24]3[CH:33]=[CH:32][C:27]([C:28](OC)=[O:29])=[CH:26][CH:25]=3)=[N:21][N:20]=2)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14](=O)[N:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)=[CH:6][N:7]=1.CC(C[AlH]CC(C)C)C.Cl.[OH-].[Na+]>C1COCC1>[NH2:1][C:2]1[C:3]([C:19]2[O:23][C:22]([C:24]3[CH:25]=[CH:26][C:27]([CH2:28][OH:29])=[CH:32][CH:33]=3)=[N:21][N:20]=2)=[N:4][C:5]([C:8]2[CH:13]=[CH:12][C:11]([CH2:14][N:15]([CH3:17])[CH3:16])=[CH:10][CH:9]=2)=[CH:6][N:7]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 14487Diisobutylaluminum hydride2×HCID 14798Sodium HydroxideHCID 59472353Methyl 4-[5-[3-amino-6-[4-(dimethylcarbamoyl)phenyl]pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]benzoate

Product 1

HCID 59472146HCID 59472146, compoundYield 33%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
10 °C

Procedure

Methyl 4-[5-[3-amino-6-[4-(dimethylcarbamoyl)phenyl]pyrazin-2-yl]-1,3,4-oxadiazol-2-yl]benzoate (154 mg, 0.3465 mmol) in dry THF (1.5 mL) was cooled in ice-bath then treated dropwise with DIBAL (346.5 μL of 1 M solution in hexanes, 0.3465 mmol). The resulting mixture was stirred 0-20° C. over 90 min and then at room temperature overnight. Additional DIBAL (1.732 mL of 1 M solution in hexanes, 1.732 mmol) was added at room temperature. The reaction mixture was poured onto water (10 mL) and acidified with 2M HCl, adjusted to pH 10 with aq NaOH solution and extracted EtOAc (6×10 mL) to give an orange solid. This was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. Product fractions were combined and passed through a bicarbonate cartridge. The eluent was concentrated in vacuo and taken up in acetonitrile and water and lypholised to leave the product as a yellow powder (13.1 mg, 33% yield); 1H NMR (400 MHz, DMSO) d 2.18 (s, 6H), 4.64 (s, 2H), 5.43 (br s, 1H), 4.43-4.45 (m, 2H), 7.65-7.63 (m, 2H), 7.69 (br s, 2H), 8.05-8.30 (m, 4H) and 8.92 (s, 1H) ppm; MS (ES+) 403.18

Workup

  1. customat room temperature
  2. customovernight
  3. additionThe reaction mixture was poured onto water (10 mL)
  4. extractionextracted EtOAc (6×10 mL)
  5. customto give an orange solid
  6. customThis was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  7. concentrationThe eluent was concentrated in vacuo

Sources & evidence

ORD record
ord-b661f9879cd6414e8dbfb76322677bd5
Source dataset
uspto-grants-2014_09
Patent number
US08841308B2

Reaction notes

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