4-Methylmorpholine → HCID 53496991, compound

HRID 77146Notes

Reaction equation

HRID 77146 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].[CH3:32][N:33]1CCO[CH2:35][CH2:34]1.CNCC.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:34]([N:33]([CH3:32])[C:3](=[O:4])[CH:2]([OH:1])[C:6]1[CH:7]=[CH:8][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:29])[F:30])[O:14][N:13]=2)=[CH:10][CH:11]=1)[CH3:35]

Participants

6

Reactant 4

HCID 79724-MethylmorpholineHCID 12219N-MethylethylamineHCID 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 53496991HCID 53496991, compoundYield 47.8%

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) was dissolved in DMF (1 mL) prior to the addition of 4-methylmorpholine (0.031 mL, 0.278 mmol), N-methylethanamine (4.93 mg, 0.083 mmol), and HATU (31.7 mg, 0.083 mmol). This was stirred overnight and was 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=12.2 min) to give (R/S)-N-ethyl-2-hydroxy-N-methyl-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (11 mg, 0.022 mmol, 47.7% yield): LCMS=473.2 [M+H]+; 1H NMR (mixture of rotamers, 400 MHz, methanol-d4) δ ppm 8.16-8.27 (2H, m), 7.48-7.75 (7 H, m), 5.54 (1 H, s), 5.51 (1 H, s), 3.35-3.55 (2 H, m), 2.96 (3 H, s), 2.91 (3 H, s), 1.11 (3 H, t, J=7.15 Hz), 0.92 (3 H, t, J=7.04 Hz).

Workup

  1. customwas then purified 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-d5e9654bddff41308387560ba333cd08
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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