Sodium Hydroxide → 1-{2-[3-(5-{5-Chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid

HRID 1942757Notes

Reaction equation

HRID 1942757 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH2:24][N:25]4[CH2:30][CH2:29][CH:28]([C:31]([O:33]CC)=[O:32])[CH2:27][CH2:26]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].[OH-].[Na+]>C(O)(C)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][N:15]=[C:14]([C:17]3[C:18]([CH2:36][CH3:37])=[C:19]([CH2:23][CH2:24][N:25]4[CH2:26][CH2:27][CH:28]([C:31]([OH:33])=[O:32])[CH2:29][CH2:30]4)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[N:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

5

Reactant 2

HCID 14798Sodium HydroxideHCID 58494002Ethyl 1-{2-[3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate

Product 1

HCID 545784631-{2-[3-(5-{5-Chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acidYield 49.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent2×

Procedure

To a solution of ethyl 1-{2-[3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylate (D112) (200 mg, 0.368 mmol) in Isopropanol (8 mL) and Water (8.00 mL) was added NaOH (3.68 mL, 1.841 mmol). The reaction was stirred at 90° C. for 2 hr before the isopropanol was removed in vacuo. The residue was acidified with aq HCl (2 M) until pH ˜2. The aqueous layer was extracted with ethyl acetate and the organic phases were dried and concentrated, purified by Mass Directed AutoPrep to afford 1-{2-[3-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-4-piperidinecarboxylic acid (E75) (93 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 1.06 (3H, t), 1.28 (6H, d), 1.68 (2H, m), 2.05 (2H, m), 2.51 (1H, m), 2.73 (2H, m), 3.07 (4H, m), 3.23 (2H, m), 3.48 (1H, m), 3.64 (1H, m), 5.37 (1H, m), 7.30 (2H, m), 7.68 (1H, d), 8.47 (1H, d), 8.81 (1H, d), 9.54 (1H, s br). δF (DMSO-d6, 376 MHz): −73.6. MS (ES): C26H31ClN4O3S requires 514.2. found 515.0 (M+H+).

Workup

  1. customwas removed in vacuo
  2. extractionThe aqueous layer was extracted with ethyl acetate
  3. customthe organic phases were dried
  4. concentrationconcentrated
  5. custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-1b6b51424db94b448ea8266e07a64c6f
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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