4-Methylmorpholine → HCID 53496732, compound

HRID 77141Notes

Reaction equation

HRID 77141 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.[CH3:32][N:33]1CCOCC1.Cl.CN.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:29])([F:30])[F:31])[O:14][N:13]=2)=[CH:8][CH:7]=1)[C:3]([NH:33][CH3:32])=[O:5]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 6364545Methylamine hydrochlorideHCID 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 53496732HCID 53496732, compoundYield 20.3%

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, 30 mg, 0.070 mmol) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.061 mL, 0.556 mmol), methanamine-HCl (4.70 mg, 0.070 mmol), and HATU (39.7 mg, 0.104 mmol). The reaction mixture was stirred overnight and then purified by preparative HPLC (PHENOMENEX® Luna 5u C18 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 10 min, 20 mL/min, 220 nM, product retention time=11.7 min) to give (R/S)-2-hydroxy-N-methyl-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (7 mg, 0.014 mmol, 20.3% yield): LCMS=445.1 [M+H]+); 1H NMR (400 MHz, methanol-d4) δ ppm 8.17 (2 H, d, J=7.92 Hz), 7.65-7.78(4 H, m), 7.49-7.66 (3 H, m), 5.12 (1 H, s), 2.79(3 H, s); HPLC Peak RT=8.3 min (Analytical Method A).

Workup

  1. custompurified by preparative HPLC (PHENOMENEX® Luna 5u
  2. washC18 21.2×100 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid
  3. customover 10 min

Sources & evidence

ORD record
ord-ba52727f3c3a49c7a913aab5d6024b89
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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