4-Methylmorpholine → HCID 53496340, compound

HRID 77206

Reaction equation

HRID 77206 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](O)=[O:4].[NH2:32][CH2:33][CH2:34][N:35]1[CH2:39][CH2:38][NH:37][C:36]1=[O:40].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:32][CH2:33][CH2:34][N:35]1[CH2:39][CH2:38][NH:37][C:36]1=[O:40])=[O:4]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 80480N-(2-Aminoethyl)ethyleneureaHCID 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 acid

Product 1

HCID 53496340HCID 53496340, compoundYield 42%

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, 25 mg, 0.058 mmol), 1-(2-aminoethyl)imidazolidin-2-one (22.46 mg, 0.087 mmol), 4-methylmorpholine (23.45 mg, 0.232 mmol), and HATU (28.7 mg, 0.075 mmol) were added to DMF (1 mL). This was stirred for 1 h before it was purified via preparative LCMS 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-(2-(2-oxoimidazolidin-1-yl)ethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (13.2 mg, 0.024 mmol, 42.0% yield): LCMS=543.1 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.11-8.23 (2 H, m), 7.54-7.73 (7 H, m), 5.11 (1 H, s), 3.32-3.49 (6 H, m), 3.21-3.29 (2 H, m); HPLC peak RT=2.4 min (Method E).

Workup

  1. customwas purified via preparative LCMS 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-769e5ec42cee471581e12be083272356
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Linked notes

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