Trifluoroacetic acid → HCID 58374103, compound

HRID 1948474Notes

Reaction equation

HRID 1948474 reaction equation
C(O[C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][C:14]([OH:16])=[O:15])=O)(C)(C)C.C(O)(C(F)(F)F)=O.[OH-].C([N+](CCCC)(CCCC)CCCC)CCC.BrC[CH:44]([C:46]1[CH:51]=[CH:50][C:49]([C:52]2[N:56]=[C:55]([C:57]3[C:61]([CH2:62][CH2:63][CH3:64])=[C:60]([C:65]4[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=4)[O:59][N:58]=3)[O:54][N:53]=2)=[CH:48][CH:47]=1)[OH:45]>C(Cl)Cl>[OH:45][CH:44]([C:46]1[CH:47]=[CH:48][C:49]([C:52]2[N:56]=[C:55]([C:57]3[C:61]([CH2:62][CH2:63][CH3:64])=[C:60]([C:65]4[CH:66]=[CH:67][CH:68]=[CH:69][CH:70]=4)[O:59][N:58]=3)[O:54][N:53]=2)=[CH:50][CH:51]=1)[CH2:6][N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][C:14]([OH:16])=[O:15]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 688605(S)-2-(1-BOC-2-pyrrolidinyl)acetic acidHCID 2723671Tetrabutylammonium HydroxideHCID 583740872-Bromo-1-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethanol

Product 1

HCID 58374103HCID 58374103, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-2-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)acetic acid (45.4 mg, 0.198 mmol) in DCM was added TFA. The reaction mixture was stirred for 1 hour followed by the removal of solvents in vacuo and drying of the solid material. Next, DMSO (2 mL) was added followed by the addition of tetrabutylammonium hydroxide (0.198 mL, 0.198 mmol) and then 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). 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); 30-100% CH3CN/water (0.1% TFA); 25 minute gradient; 30 mL/min. Isolated fractions with correct mass were freeze-dried overnight to yield 9 mg of 2-((2S)-1-(2-hydroxy-2-(4-(5-(5-phenyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)phenyl)ethyl)pyrrolidin-2-yl)acetic acid as a TFA salt. 1H NMR (400 MHz, MeOH-d3) δ ppm 8.18 (4H, d, J=8.35 Hz), 7.77-7.84 (2H, m), 7.54-7.67 (5H, m), 5.92-6.01 (1H, m), 5.00-5.09 (2H, m), 4.26-4.42 (1H, m), 3.76-3.94 (1H, m), 3.00-3.11 (2H, m), 2.75-2.98 (2H, m), 2.18-2.34 (1H, m), 1.90-2.14 (2H, m), 1.60-1.85 (3H, t, J=7.25 Hz). MS (m+1)=503. HPLC Peak RT=3.50 minutes (Analytical Method A). Purity=90%.

Workup

  1. customfollowed by the removal of solvents in vacuo
  2. customdrying of the solid material
  3. additionNext, DMSO (2 mL) was added
  4. filtrationThe reaction mixture was filtered
  5. custompurified by HPLC
  6. custom25 minute
  7. customIsolated fractions with correct mass were freeze-dried overnight

Sources & evidence

ORD record
ord-0dc1193f9203437fa1d177e64a4f0f65
Source dataset
uspto-grants-2013_03
Patent number
US08399451B2

Reaction notes

Loading…