Acetic Acid → 1-{[3-(5-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-3 azetidinecarboxylic acid

HRID 1942729Notes

Reaction equation

HRID 1942729 reaction equation
[CH2:1]([C:3]1[C:8]([CH:9]=O)=[CH:7][CH:6]=[CH:5][C:4]=1[C:11]1[N:15]=[C:14]([C:16]2[CH:17]=[CH:18][C:19]([O:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=2)[C:21]#[N:22])[S:13][N:12]=1)[CH3:2].[NH:28]1[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CO>[C:21]([C:20]1[CH:23]=[C:16]([C:14]2[S:13][N:12]=[C:11]([C:4]3[C:3]([CH2:1][CH3:2])=[C:8]([CH2:9][N:28]4[CH2:31][CH:30]([C:32]([OH:34])=[O:33])[CH2:29]4)[CH:7]=[CH:6][CH:5]=3)[N:15]=2)[CH:17]=[CH:18][C:19]=1[O:24][CH:25]([CH3:27])[CH3:26])#[N:22]

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 931923-azetidinecarboxylic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 866590045-[3-(2-Ethyl-3-formylphenyl)-1,2,4-thiadiazol-5-yl]-2-[(1-methylethyl)oxy]benzonitrile

Product 1

HCID 545795921-{[3-(5-{3-Cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-3 azetidinecarboxylic acidYield 27.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-[3-(2-ethyl-3-formylphenyl)-1,2,4-thiadiazol-5-yl]-2-[(1-methylethyl)oxy]benzonitrile (D46) (110 mg) in dichloromethane (DCM) (5 mL) and methanol (5.00 mL) was added 3-azetidinecarboxylic acid (147 mg) and acetic acid (0.050 mL). The resulting solution was stirred at room temperature for overnight. Sodium triacetoxyborohydride (185 mg) was added and the reaction solution was stirred for 2 h. The solvent was removed in vacuo and the residue was purified by Mass Directed AutoPrep to give 1-{[3-(5-{3-cyano-4-[(1-methylethyl)oxy]phenyl}-1,2,4-thiadiazol-3-yl)-2-ethylphenyl]methyl}-3 azetidinecarboxylic acid (E17) (37 mg) as a TFA salt (white solid). δH (DMSO-d6, 400 MHz): 1.03 (3H, t), 1.31 (6H, d), 2.93 (2H, q), 3.60 (1H, m), 4.22 (4H, m), 4.52 (2H, s), 4.89 (1H, m), 7.38 (1H, t), 7.42 (1H, d), 7.51 (1H, s br), 7.82 (1H, d), 8.27 (1H, dd), 8.42 (1H, d), 10.20 (1H, s br), 13.13 (1H, br s). δF (DMSO-d6, 376 MHz): −73.7. MS (ES): C26H26N4O3S requires 462. found 463.2 (M+H+).

Workup

  1. stirringthe reaction solution was stirred for 2 h
  2. customThe solvent was removed in vacuo
  3. customthe residue was purified by Mass Directed AutoPrep

Sources & evidence

ORD record
ord-e7f3a399e55a4368b99de62c3de60598
Source dataset
uspto-grants-2013_03
Patent number
US08389508B2

Reaction notes

Loading…