2-Morpholineacetic acid → 2-(4-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)morpholin-2-yl)acetic acid

HRID 1948522Notes

Reaction equation

HRID 1948522 reaction equation
[O:1]1[CH2:3][CH:2]1[C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)[C:16]=3[C:26]([F:29])([F:28])[F:27])[O:12][N:11]=2)=[CH:6][CH:5]=1.[NH:30]1[CH2:35][CH2:34][O:33][CH:32]([CH2:36][C:37]([OH:39])=[O:38])[CH2:31]1>CC(O)C.CS(C)=O>[OH:1][CH:2]([C:4]1[CH:9]=[CH:8][C:7]([C:10]2[N:14]=[C:13]([C:15]3[O:19][N:18]=[C:17]([C:20]4[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=4)[C:16]=3[C:26]([F:28])([F:27])[F:29])[O:12][N:11]=2)=[CH:6][CH:5]=1)[CH2:3][N:30]1[CH2:35][CH2:34][O:33][CH:32]([CH2:36][C:37]([OH:39])=[O:38])[CH2:31]1

Participants

5

Reactant 2

HCID 50462442-Morpholineacetic acidHCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 509237062-(4-(2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)morpholin-2-yl)acetic acid

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 3776IsopropanolSolvent

Procedure

To a mixture of 3-(4-(oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole, Preparation 28C (25 mg, 0.063 mmol) in 2-propanol (2 mL) and DMSO (1 mL) was added 2-(morpholin-2-yl)acetic acid (18.18 mg, 0.125 mmol). The reaction mixture was hated at 80° C. overnight. The crude material was purified via preparative LC/MS with the following conditions: Column: Waters XBridge C18, 19×250 mm, 5-μm particles; Guard Column: Waters XBridge C18, 19×10 mm, 5-μm particles; Mobile Phase A: 5:95 acetonitrile:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 acetonitrile:water with 10-mM ammonium acetate; Gradient: 15-100% B over 25 minutes, then a 5-minute hold at 100% B; Flow: 20 mL/min. Fractions containing the desired product were combined and dried via centrifugal evaporation. The yield of the desired product was 12.8 mg, and its purity was 99%. 1H NMR (400 MHz, MeOD) δ ppm 8.18 (2H, d, J=8.28 Hz), 7.38-7.86 (7H, m), 5.03 (1H, ddd, J=9.03, 4.39, 4.14 Hz), 3.97-4.11 (1H, m), 3.90 (1H, t, J=9.66 Hz), 3.69-3.84 (1H, m), 2.97-3.21 (2H, m), 2.69-2.93 (2H, m), 2.18-2.63 (4H, m). MS (m+1)=545.

Workup

  1. customThe crude material was purified via preparative LC/MS with the following conditions
  2. waitGradient: 15-100% B over 25 minutes
  3. customa 5-minute hold
  4. additionFractions containing the desired product
  5. customdried via centrifugal evaporation

Sources & evidence

ORD record
ord-4914f618ba374c078bced820c996438b
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…