Sodium Hydroxide → 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-L-proline

HRID 1942754Notes

Reaction equation

HRID 1942754 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]([CH2:26][CH3:27])=[C:19]([CH2:23][CH:24]=O)[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10].C([O-])(=O)C.[Na+].Cl.[NH:34]1[CH2:42][CH2:41][CH2:40][C@H:35]1[C:36]([O:38]C)=[O:37].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl.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]([CH2:26][CH3:27])=[C:19]([CH2:23][CH2:24][N:34]4[CH2:42][CH2:41][CH2:40][C@H:35]4[C:36]([OH:38])=[O:37])[CH:20]=[CH:21][CH:22]=3)[N:13]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH:9]([CH3:11])[CH3:10]

Participants

8

Reactant 5

HCID 14798Sodium HydroxideHCID 517045Sodium AcetateHCID 2733200methyl L-prolinate hydrochlorideHCID 5049666Sodium triacetoxyborohydrideHCID 58494142[3-(5-{3-Chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]acetaldehyde

Product 1

HCID 545780291-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-L-prolineYield 40.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 21889133Propan-2-ol--water (1/1)Solvent

Procedure

To a solution of [3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]acetaldehyde (D52) (110 mg, 0.274 mmol) in Dichloromethane (DCM) (10 mL) was added sodium acetate (33.8 mg, 0.412 mmol) and hydrogen chloride-methyl L-prolinate (1:1) (68.2 mg, 0.412 mmol). After 5 minutes, sodium triacetoxyborohydride (87 mg, 0.412 mmol) was added and the reaction solution was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was hydrolized by NaOH (2.74 mL, 1.372 mmol) in isopropanol/water (10 mL, 1:1). The residue was purified by Mass Directed AutoPrep to afford 1-{2-[3-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]ethyl}-L-proline (E65) (56 mg) as a TFA salt.

Workup

  1. customThe solvent was removed in vacuo
  2. customThe residue was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-ed665942fabc41079a24dd7a3ae2ad6c
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

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