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

HRID 712371Notes

Reaction equation

HRID 712371 reaction equation
[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:14][C:13]([C:22]3[S:26][N:25]=[C:24]([N:27]4[CH2:32][CH2:31][C:30]([CH3:38])([C:33]([O:35]CC)=[O:34])[CH2:29][CH2:28]4)[N:23]=3)=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2].[OH-].[Na+]>CCO>[CH2:1]([NH:3][C:4]([NH:6][C:7]1[S:8][C:9]2[C:15]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)=[CH:14][C:13]([C:22]3[S:26][N:25]=[C:24]([N:27]4[CH2:28][CH2:29][C:30]([CH3:38])([C:33]([OH:35])=[O:34])[CH2:31][CH2:32]4)[N:23]=3)=[CH:12][C:10]=2[N:11]=1)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86664068HCID 86664068, compound

Product 1

HCID 727230791-(5-{2-[(Ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-3-yl)-4-methylpiperidine-4-carboxylic acidYield 34%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

Ethyl 1-(5-{2-[(ethylcarbamoyl)amino]-7-(pyridin-2-yl)-1,3-benzothiazol-5-yl}-1,2,4-thiadiazol-3-yl)-4-methylpiperidine-4-carboxylate (100 mg, 0.13 mmol) was dissolved in EtOH (10 mL) and 2M aqueous NaOH (2.5 mL) was added and the mixture stirred at 90° C. for 18 h, cooled to rt and concentrated to ˜⅕ volume water (10 mL) and DCM (10 mL) added. The aqueous layer was separated and the organic layer discarded. The resultant aqueous layer was acidified to pH˜2 and extracted with DCM (3×10 mL), the combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to give a brown solid which was purified by flash column chromatography (2× Biotage, SP4, 12 g, 2-8% MeOH, DCM) to afford Compound 233 as a cream solid (23 mg, 34%). 1H NMR (CDCl3) δ 8.70 (dd, J=4.8, 0.8 Hz, 1H), 8.62 (d, J=1.4 Hz, 1H), 8.44 (d, J=1.3 Hz, 1H), 8.09 (d, J=8.2 Hz, 1H), 7.78 (td, J=7.8, 1.8 Hz, 1H), 7.22 (ddd, J=7.4, 4.9, 0.8 Hz, 1H), 3.83 (brs, 2H), 3.39-3.29 (m, 5H), 2.22 (d, J=13.3 Hz, 2H), 1.70-1.40 (m, 4H), 1.19 (t, J=7.3 Hz, 4H), 0.86 (t, J=7.5 Hz, 3H). MS: 524.06 [M+H]+.

Workup

  1. temperaturecooled to rt
  2. concentrationconcentrated
  3. additionadded
  4. customThe aqueous layer was separated
  5. extractionextracted with DCM (3×10 mL)
  6. dry with materialthe combined organic layers were dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto give a brown solid which
  10. customwas purified by flash column chromatography (2× Biotage, SP4, 12 g, 2-8% MeOH, DCM)

Sources & evidence

ORD record
ord-d70ff2c166804e99a0882c5e49e9a6d8
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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