Cesium carbonate → HCID 50923705, compound

HRID 1948521Notes

Reaction equation

HRID 1948521 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.[OH:30][CH:31]1[CH2:36][NH:35][CH2:34][CH:33]([C:37]([OH:39])=[O:38])[CH2:32]1.C(=O)([O-])[O-].[Cs+].[Cs+]>CC(O)C.CS(C)=O>[OH:30][CH:31]1[CH2:36][N:35]([CH2:3][CH:2]([OH:1])[C:4]2[CH:5]=[CH:6][C:7]([C:10]3[N:14]=[C:13]([C:15]4[O:19][N:18]=[C:17]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[C:16]=4[C:26]([F:27])([F:28])[F:29])[O:12][N:11]=3)=[CH:8][CH:9]=2)[CH2:34][CH:33]([C:37]([OH:39])=[O:38])[CH2:32]1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 4577144HCID 4577144, compound2×HCID 866563983-(4-(Oxiran-2-yl)phenyl)-5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazole

Product 1

HCID 50923705HCID 50923705, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 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) and 5-hydroxypiperidine-3-carboxylic acid (21.81 mg, 0.150 mmol) in 2-propanol (2 mL) and DMSO (2.000 mL) was added cesium carbonate (122 mg, 0.376 mmol). The reaction mixture was heated at 80° C. Next, 5-hydroxypiperidine-3-carboxylic acid (21.81 mg, 0.150 mmol) was added and the reaction was checked after 4 hr. Product peak was observed but starting material remained. The reaction mixture was heated 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 5.6 mg, and its purity was 99%. 1H NMR (400 MHz, MeOD) δ ppm 8.21 (2H, d, J=7.78 Hz), 7.69 (4H, d, J=6.78 Hz), 7.53-7.65 (3H, m), 5.19 (1H, dt, J=10.10, 3.61 Hz), 4.16 (1H, br. s.), 3.08-3.26 (5H, m), 2.86-3.06 (2H, m), 1.87-2.06 (3H, m). MS (m+1)=545.

Workup

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

Sources & evidence

ORD record
ord-a662290ef35841158298c4042d2f0cc9
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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