1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 50925182, compound

HRID 1948473Notes

Reaction equation

HRID 1948473 reaction equation
Br[CH2:2][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[C:20]([CH2:21][CH2:22][CH3:23])=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:18][N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)[OH:4].[CH2:30]1[C@H:33]([C:34]([OH:36])=[O:35])[NH:32][CH2:31]1.C1CCN2C(=NCCC2)CC1>CS(C)=O>[OH:4][CH:3]([C:5]1[CH:10]=[CH:9][C:8]([C:11]2[N:15]=[C:14]([C:16]3[C:20]([CH2:21][CH2:22][CH3:23])=[C:19]([C:24]4[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=4)[O:18][N:17]=3)[O:13][N:12]=2)=[CH:7][CH:6]=1)[CH2:2][N:32]1[CH2:31][CH2:30][C@@H:33]1[C:34]([OH:36])=[O:35]

Participants

5

Reactant 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 637601D-Azetidine-2-carboxylic acidHCID 583740872-Bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Product 1

HCID 50925182HCID 50925182, compound

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 2-bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol, Preparation 1C (30 mg, 0.066 mmol) and D-Azetidine-2-carboxylic acid (20.03 mg, 0.198 mmol) in DMSO (2 mL) was added DBU (0.030 mL, 0.198 mmol). The reaction mixture was heated at 80° C. for 2 hours. The reaction mixture was filtered and purified by HPLC. HPLC conditions: PHENOMENEX® Luna C18 5 micron column (250×30mm); 25-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 16 mg of (2R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl) azetidine-2-carboxylic acid as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.14 (2H, dd, J=8.57, 2.86 Hz), 7.82 (2H, dd, J=8.02, 1.65 Hz), 7.58-7.70 (5H, m), 5.16-5.29 (1H, m), 4.89-5.10 (1H, m), 3.84-4.05 (2H, m), 3.18-3.41 (2H, m), 2.96-3.03 (2H, m), 2.51-2.61 (1H, m), 1.63-1.76 (2H, m), 0.97 (3H, t, K=7.25 Hz). MS (m+1)=475. HPLC Peak RT=3.5 minutes (Analytical Method A). Purity=90%.

Workup

  1. filtrationThe reaction mixture was filtered
  2. custompurified by HPLC
  3. custom25 minute
  4. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-a574be2d71ea47fb9981c1dda651213d
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

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