Sodium Hydroxide → 4-Ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]thiazol-2-yl]piperidine-4-carboxylic acid

HRID 712351Notes

Reaction equation

HRID 712351 reaction equation
[CH2:1]([C:3]1([C:35]([O:37]CC)=[O:36])[CH2:8][CH2:7][N:6]([C:9]2[S:10][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)=[CH:12][N:13]=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:10][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)=[CH:12][N:13]=2)[CH2:5][CH2:4]1)[CH3:2]

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86664058HCID 86664058, compound

Product 1

HCID 866640594-Ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]thiazol-2-yl]piperidine-4-carboxylic acid

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
70 °C

Procedure

To a solution of ethyl 4-ethyl-1-[5-[2-(ethylcarbamoylamino)-7-(2-pyridyl)-1,3-benzothiazol-5-yl]thiazol-2-yl]piperidine-4-carboxylate (30 mg, 0.053 mmol) in EtOH (1 mL) was added aqueous NaOH (0.3 mL, 3.5 M). The solution was heated to 70° C. for 22 h then cooled to rt and the pH of the solution adjusted to 4-5. The mixture was extracted with EtOAc (3×1 mL) and the combined organic layer dried over Na2SO4, filtered then evaporated under reduced pressure. The residue was adsorbed to a 0.5 g silica plug then purified using a 4 g silica column, using a MeOH:DCM elution gradient. Compound 221 was isolated as an off-white solid (2.0 mg, 11% yield). 1H NMR (MeOD) δ 8.75 (ddd, J=4.8, 1.8, 0.9 Hz, 1H), 8.20 (d, J=8.3 Hz, 1H), 8.00 (d, J=1.6 Hz, 1H), 7.97-7.90 (m, 1H), 7.73 (d, J=1.6 Hz, 1H), 7.59 (s, 1H), 7.38 (ddd, J=7.5, 4.9, 0.9 Hz, 1H), 3.87 (dd, J=9.6, 3.7 Hz, 2H), 3.39-3.32 (m, 2H), 3.25 (td, J=13.3, 2.9 Hz, 2H), 2.23 (d, J=13.3 Hz, 2H), 1.64 (q, J=7.5 Hz, 2H), 1.61-1.52 (m, 2H), 1.23 (t, J=7.2 Hz, 3H), 0.92 (t, J=7.5 Hz, 3H). MS: 537.13 [M+H]+.

Workup

  1. temperaturethen cooled to rt
  2. extractionThe mixture was extracted with EtOAc (3×1 mL)
  3. dry with materialthe combined organic layer dried over Na2SO4
  4. filtrationfiltered
  5. customthen evaporated under reduced pressure
  6. customthen purified
  7. washDCM elution gradient

Sources & evidence

ORD record
ord-bed6b415a01d413a9f82ee5a66fc61f4
Source dataset
uspto-grants-2015_11
Patent number
US09181234B2

Reaction notes

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