Hydrochloric Acid → 3-{4-[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]-1-piperidinyl}propanoic acid

HRID 1942762Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:29][CH3:30])=[C:19]([CH:23]4[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]4)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C1CCN2C(=NCCC2)CC1.[C:42]([O:46]CC)(=[O:45])[CH:43]=[CH2:44].[OH-].[Na+].Cl>C(#N)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:12]2[S:16][C:15]([C:17]3[C:18]([CH2:29][CH3:30])=[C:19]([CH:23]4[CH2:28][CH2:27][N:26]([CH2:44][CH2:43][C:42]([OH:46])=[O:45])[CH2:25][CH2:24]4)[CH:20]=[CH:21][CH:22]=3)=[N:14][N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of 4-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]piperidine (D120) (200 mg, 0.452 mmol) in Acetonitrile (10 mL) was added DBU (0.205 mL, 1.357 mmol) and ethyl 2-propenoate (136 mg, 1.357 mmol). The reaction solution was heated to 60° C. for 2 h. The reaction solution was concentrated and the residue was hydrolized with a solution of NaOH (4.52 mL, 2.262 mmol) in water. The reaction mixture was neutralized with 2N HCl till pH ˜6.0. The mixture was extracted with EA/THF for 3 times. The combined organic layers were concentrated and purified by Mass Directed AutoPrep to afford 3-{4-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,3,4-thiadiazol-2-yl)-2-ethylphenyl]-1-piperidinyl}propanoic acid (E95) (12 mg) as a TFA salt.

Workup

concentrationThe reaction solution was concentrated
extractionThe mixture was extracted with EA/THF for 3 times
concentrationThe combined organic layers were concentrated
custompurified by Mass Directed AutoPrep

Sources & evidence

ORD record: ord-4e65a6069c9c48c29db6b946e8397049
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08389508B2

Reaction notes

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