1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 50923276, compound

HRID 1948471Notes

Reaction equation

HRID 1948471 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([OH:16])=[O:15])[CH2:9]1)=O)(C)(C)C.C(O)(C(F)(F)F)=O.C(Cl)Cl.C1CCN2C(=NCCC2)CC1.BrC[CH:40]([C:42]1[CH:47]=[CH:46][C:45]([C:48]2[N:52]=[C:51]([C:53]3[C:57]([CH2:58][CH2:59][CH3:60])=[C:56]([C:61]4[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=4)[O:55][N:54]=3)[O:50][N:49]=2)=[CH:44][CH:43]=1)[OH:41]>>[OH:41][CH:40]([C:42]1[CH:43]=[CH:44][C:45]([C:48]2[N:52]=[C:51]([C:53]3[C:57]([CH2:58][CH2:59][CH3:60])=[C:56]([C:61]4[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=4)[O:55][N:54]=3)[O:50][N:49]=2)=[CH:46][CH:47]=1)[CH2:6][N:8]1[CH2:13][CH2:12][CH2:11][C@@H:10]([C:14]([OH:16])=[O:15])[CH2:9]1

Participants

5

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 6435161-(1,1-Dimethylethyl) (3R)-1,3-piperidinedicarboxylateHCID 21863450Trifluoroacetic acid methylene chlorideHCID 583740872-Bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Product 1

HCID 50923276HCID 50923276, compound

Conditions

Temperature
80 °C

Procedure

To (R)-1-(tert-butoxycarbonyl)piperidine-3-carboxylic acid (45.4 mg, 0.198 mmol) was added TFA/DCM (1:1). The mixture was stirred for 1 hour and solvent was removed solvent in vacuo, followed by chasing once with DCM. The resulting mixture was dried in vacuo. This crude residue was dissolved in DMSO (2 mL) and DBU (0.060 mL, 0.396 mmol) was added. After 5 minutes, 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) was added. 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); 20-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 6 mg of (3R)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)piperidine-3-carboxylic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.21 (2H, d, J=7.91 Hz), 7.71 (2H, dd, J=8.02, 1.65 Hz), 7.47-7.56 (5H, m), 4.46 (1H, br. s.), 4.10 (2H, d, J=6.37 Hz), 3.25-3.61 (2H, m), 2.92-3.03 (3H, m), 2.91 (2H, br. s.), 2.01-2.27 (1H, m), 1.81-2.00 (3H, m), 1.60-1.76 (2H, m, J=7.61, 7.61, 7.61, 7.61, 7.36 Hz), 1.20-1.59 (1H, m), 0.95 (3H, t, J=7.36 Hz). MS (m+1)=503. HPLC Peak RT=3.32 minutes (Analytical Method A). Purity=96%.

Workup

  1. customsolvent was removed solvent in vacuo
  2. customThe resulting mixture was dried in vacuo
  3. dissolutionThis crude residue was dissolved in DMSO (2 mL)
  4. waitAfter 5 minutes
  5. additionwas added
  6. filtrationThe reaction mixture was filtered
  7. custompurified by HPLC
  8. custom25 minute
  9. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-ed434d6bbd75471d83d27572a91edfb0
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…