Sodium Hydroxide → HCID 89962654, compound

HRID 877425Notes

Reaction equation

HRID 877425 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:22]=[CH:21][C:11]3[N:12]=[C:13]([CH2:15][C:16]([O:18]CC)=O)[S:14][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.[OH-].[Na+].Cl.[CH3:26][C:27]1[O:31][C:30]([CH2:32][NH2:33])=[N:29][N:28]=1.C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F>C1COCC1.O>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:22]=[CH:21][C:11]3[N:12]=[C:13]([CH2:15][C:16]([NH:33][CH2:32][C:30]4[O:31][C:27]([CH3:26])=[N:28][N:29]=4)=[O:18])[S:14][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 2724699PyBOPHCID 208480101-(5-Methyl-1,3,4-oxadiazol-2-yl)methanamine--hydrogen chloride (1/1)HCID 89962199HCID 89962199, compound

Product 1

HCID 89962654HCID 89962654, compoundYield 80%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Ethyl 2-(6-(4-fluorophenyl)benzo[d]thiazol-2-yl)acetate (described in WO2011/074560, 500 mg, 1.59 mmol) in THF (4 mL) was treated with sodium hydroxide (1N NaOH, 1.9 mL, 1.9 mmol). After 2 hours, the reaction mixture was concentrated to dryness under reduced pressure. The residue was co-evaporated with toluene (5 mL), re-dissolved in DMF (4 mL), and treated with (5-methyl-1,3,4-oxadiazol-2-yl)methanamine hydrochloride (284 mg, 1.90 mmol), TEA (2.2 mL, 16 mmol) and PyBOP (990 mg, 1.9 mmol). After 16 hours, the reaction mixture was diluted with water (20 mL), extracted with DCM (3×10 mL), dried over Na2SO4 and concentrated under reduced pressure. The residue was purified by silica gel (eluting with 0-20% DCM/MeOH) to give Compound A9a (485 mg, 80.0% yield) as an oil.

Workup

  1. concentrationthe reaction mixture was concentrated to dryness under reduced pressure
  2. dissolutionre-dissolved in DMF (4 mL)
  3. waitAfter 16 hours
  4. extractionextracted with DCM (3×10 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel (eluting with 0-20% DCM/MeOH)
  8. customto give Compound A9a (485 mg, 80.0% yield) as an oil

Sources & evidence

ORD record
ord-515f61b7547c4a1daf913d6f27260eb5
Source dataset
uspto-grants-2015_03
Patent number
US08987314B2

Reaction notes

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