Sodium Hydroxide → 4-Ethyl-1-(3-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-5-yl)piperidine-4-carboxylic acid

HRID 712368Notes

Reaction equation

HRID 712368 reaction equation
[CH2:1]([C:3]1([C:35]([O:37]CC)=[O:36])[CH2:8][CH2:7][N:6]([C:9]2[S:13][N:12]=[C:11]([C:14]3[CH:15]=[C:16]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[C:17]4[S:21][C:20]([NH:22][C:23](=[O:27])[NH:24][CH2:25][CH3:26])=[N:19][C:18]=4[CH:28]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2].[OH-].[Na+]>CCO>[CH2:1]([C:3]1([C:35]([OH:37])=[O:36])[CH2:8][CH2:7][N:6]([C:9]2[S:13][N:12]=[C:11]([C:14]3[CH:15]=[C:16]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=4)[C:17]4[S:21][C:20]([NH:22][C:23](=[O:27])[NH:24][CH2:25][CH3:26])=[N:19][C:18]=4[CH:28]=3)[N:10]=2)[CH2:5][CH2:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86664065HCID 86664065, compound

Product 1

HCID 866640664-Ethyl-1-(3-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-5-yl)piperidine-4-carboxylic acidYield 38%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Ethyl 4-ethyl-1-(3-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-5-yl)piperidine-4-carboxylate (70 mg, 0.09 mmol) was dissolved in EtOH (15 mL) and 2M aqueous NaOH (5 mL) and stirred at 90° C. for 18 h. The reaction was cooled to rt and concentrated to ˜⅕ volume. Water (10 mL) and DCM (10 mL) were added and the aqueous layer separated, the organic layer discarded and the aqueous layer acidified to pH˜2 and extracted with DCM (3×10 mL). The organic layers were combined, dried (MgSO4), filtered and concentrated in vacuo to give a brown solid, which was purified by flash column chromatography (Biotage, SP4, 12 g, 2-8% MeOH, DCM) to afford Compound 232 as a cream solid (18 mg, 38%).

Workup

  1. concentrationconcentrated
  2. additionWater (10 mL) and DCM (10 mL) were added
  3. customthe aqueous layer separated
  4. extractionextracted with DCM (3×10 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customto give a brown solid, which
  9. customwas purified by flash column chromatography (Biotage, SP4, 12 g, 2-8% MeOH, DCM)

Sources & evidence

ORD record
ord-da5241bda274407aaffcb539f591ae8b
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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