4-Methylmorpholine → HCID 178430881, compound

HRID 77223Notes

Reaction equation

HRID 77223 reaction equation
[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([OH:5])=O.Cl.[CH3:33][C:34]1[N:35]=[C:36]([CH2:39][NH2:40])[NH:37][CH:38]=1.CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[OH:1][CH:2]([C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:16]=[C:15]([C:17]3[O:21][N:20]=[C:19]([C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)[C:18]=3[C:28]([F:31])([F:30])[F:29])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([NH:40][CH2:39][C:36]1[NH:37][CH:38]=[C:34]([CH3:33])[N:35]=1)=[O:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 674589572-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acidHCID 178430883HCID 178430883, compound

Product 1

HCID 178430881HCID 178430881, compoundYield 21.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

(R/S)-2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Int-V, 20 mg, 0.046 mmol), C-(4-methyl-1H-imidazol-2-yl)-methylamine hydrochloride (5.15 mg, 0.046 mmol), 4-methylmorpholine (18.76 mg, 0.185 mmol), and HATU (22.92 mg, 0.060 mmol) were dissolved in DMF (1 mL). This was stirred for 1 h before it 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 methanol:water with 10-mM ammonium acetate; Mobile Phase B: 95:5 methanol: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 to give (R/S)-2-hydroxy-N-((4-methyl-1H-imidazol-2-yl)methyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (5.5 mg, 10.07 μmol, 21.71% yield): LCMS=525.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.15 (2 H, d, J=8.53 Hz), 7.48-7.72 (8 H, m), 6.64 (1 H, d, J=1.00 Hz), 5.17 (1 H, s), 4.28-4.53 (2 H, m), 2.18 (3H, d, J=1.00 Hz); HPLC peak RT=2.5 min (Method E).

Workup

  1. customwas 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-ca41ed2fc0f340de8fceb48b75b2a2bc
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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