Sodium Acetate → 1-[(3-{5-[3-Cyano-4-(2-methylpropyl)phenyl]-1,2,4-thiadiazol-3-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylic acid

HRID 1942735Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1942735
[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]([CH2:24][CH:25]([CH3:27])[CH3:26])=[C:20]([CH:23]=2)[C:21]#[N:22])[S:13][N:12]=1)[CH3:2].C([O-])(=O)C.[Na+].Cl.[NH:34]1[CH2:37][CH:36]([C:38]([O:40]C)=[O:39])[CH2:35]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C>[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:34]4[CH2:37][CH:36]([C:38]([OH:40])=[O:39])[CH2:35]4)[CH:7]=[CH:6][CH:5]=3)[N:15]=2)[CH:17]=[CH:18][C:19]=1[CH2:24][CH:25]([CH3:27])[CH3:26])#[N:22]

Komponenten

7

Edukt 4

HCID 517045Sodium AcetateHCID 5049666Sodium triacetoxyborohydrideHCID 21100040Methyl azetidine-3-carboxylate hydrochlorideHCID 584941545-[3-(2-Ethyl-3-formylphenyl)-1,2,4-thiadiazol-5-yl]-2-(2-methylpropyl)benzonitrile

Produkt 1

HCID 545765011-[(3-{5-[3-Cyano-4-(2-methylpropyl)phenyl]-1,2,4-thiadiazol-3-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylic acidAusbeute 41,6 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 176Acetic AcidKatalysatorHCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a solution of 5-[3-(2-ethyl-3-formylphenyl)-1,2,4-thiadiazol-5-yl]-2-(2-methylpropyl)benzonitrile (D63) (100 mg) in dichloromethane (DCM) (15 mL) was added sodium acetate (22.9 mg), hydrogen chloride-methyl 3-azetidinecarboxylate (1:1) (42.4 mg) and 5 drops of acetic acid. After stirring for 30 min, sodium triacetoxyborohydride (85 mg) was added and the reaction solution was stirred at room temperature overnight. The solvent was removed in vacuo and the residue was dissolved in ethyl acetate (30 mL), the organic phase was washed with water, dried over sodium sulphate and concentrated. The residue was dissolved in isopropanol/water (10 mL, 1:1), 0.5M sodium hydroxide (2.66 mL) was added. The reaction solution was stirred at room temperature overnight. The isopropanol was removed in vacuo and the residue was acidified to pH=3-4. The resulting solution was extracted with ethyl acetate (2*15 mL), and the combined organic phases were dried over sodium sulphate, concentrated and purified by Mass Directed AutoPrep to afford 1-[(3-{5-[3-cyano-4-(2-methylpropyl)phenyl]-1,2,4-thiadiazol-3-yl}-2-ethylphenyl)methyl]-3-azetidinecarboxylic acid (E27) (51 mg) as a TFA salt. δH (DMSO-d6, 400 MHz): 0.87 (6H, d), 1.04 (3H, t), 1.93 (1H, m), 2.71 (2H, d), 2.92 (2H, q), 3.58 (1H, m), 4.20 (4H, m), 4.51 (2H, s), 7.39 (1H, t), 7.52 (1H, d), 7.64 (1H, d), 7.84 (1H, d), 8.26 (1H, dd), 8.47 (1H, d). δF (DMSO-d6, 376 MHz): −73.5. MS (ES): C26H28N4O2S requires 460. found 461.1 (M+H+).

Aufarbeitung

  1. stirringthe reaction solution was stirred at room temperature overnight
  2. customThe solvent was removed in vacuo
  3. dissolutionthe residue was dissolved in ethyl acetate (30 mL)
  4. washthe organic phase was washed with water
  5. dry with materialdried over sodium sulphate
  6. concentrationconcentrated
  7. dissolutionThe residue was dissolved in isopropanol/water (10 mL, 1:1)
  8. addition0.5M sodium hydroxide (2.66 mL) was added
  9. stirringThe reaction solution was stirred at room temperature overnight
  10. customThe isopropanol was removed in vacuo
  11. extractionThe resulting solution was extracted with ethyl acetate (2*15 mL)
  12. dry with materialthe combined organic phases were dried over sodium sulphate
  13. concentrationconcentrated
  14. custompurified by Mass Directed AutoPrep

Quellen und Nachweise

ORD-Eintrag
ord-40af94e790f940e09b6bed5fd3b1694a
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08389508B2

Notizen zur Reaktion

Wird geladen…