Dimethyl Sulfoxide → 2-(3-(2-Hydroxyethyl)piperidin-1-yl)-1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

HRID 1948520Notes

Reaction equation

HRID 1948520 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][CH2:33][CH:32]([CH2:36][CH2:37][OH:38])[CH2:31]1.CS(C)=O>CC(O)C>[OH:38][CH2:37][CH2:36][CH:32]1[CH2:33][CH2:34][CH2:35][N:30]([CH2:3][CH:2]([C:4]2[CH:9]=[CH:8][C:7]([C:10]3[N:14]=[C:13]([C:15]4[O:19][N:18]=[C:17]([C:20]5[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=5)[C:16]=4[C:26]([F:27])([F:28])[F:29])[O:12][N:11]=3)=[CH:6][CH:5]=2)[OH:1])[CH2:31]1

Participants

5

Reactant 3

HCID 679Dimethyl SulfoxideHCID 27627163-PiperidineethanolHCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 509237042-(3-(2-Hydroxyethyl)piperidin-1-yl)-1-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

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 (30 mg, 0.075 mmol) in 2-propanol (2 mL) was added 2-(piperidin-3-yl)ethanol (19.41 mg, 0.150 mmol). The reaction mixture was heated to 80° C. DMSO (1 mL) was added to help solubilize. The reaction mixture was stirred 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 MeOH:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 MeOH:water with 10-mM ammonium acetate; Gradient: 45-100% 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 Example 31 was 13.0 mg, and its purity was 100%. 1H NMR (400 MHz, MeOD) δ ppm 8.18 (2H, d, J=8.03 Hz), 7.52-7.75 (7H, m), 5.01 (1H, ddd, J=8.60, 4.20, 4.02 Hz), 3.54-3.72 (2H, m), 3.13 (2H, br. s.), 2.73 (2H, br. s.), 2.32 (1H, br. s.), 2.11 (1H, br. s.), 1.61-1.92 (4H, m), 1.48 (2H, dd, J=13.68, 6.90 Hz), 1.04 (1H, br. s.). MS (m+1)=529.

Workup

  1. customThe crude material was purified via preparative LC/MS with the following conditions
  2. waitGradient: 45-100% 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-3947e81958fb48bbaaf3ac9e42fe2345
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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