Ethanolamine → 2-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide

HRID 77193Notes

Reaction equation

HRID 77193 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.[NH2:32][CH2:33][CH2:34][OH:35].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: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:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[C:18]=3[C:28]([F:29])([F:30])[F:31])[O:14][N:13]=2)=[CH:10][CH:11]=1)[C:3]([NH:32][CH2:33][CH2:34][OH:35])=[O:5]

Participants

6

Reactant 4

HCID 700EthanolamineHCID 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 acid

Product 1

HCID 534964592-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamideYield 56.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-Hydroxy-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetic acid (Ex-Va, 60 mg, 0.139 mmol), 2-aminoethanol (12.75 mg, 0.209 mmol), 4-methylmorpholine (56.3 mg, 0.556 mmol), and HATU (68.8 mg, 0.181 mmol) were added to DMF (1 mL). The mixture was stirred for 1 h before it was purified by prep HPLC (PHENOMENEX® Luna 5u 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 25 mL/min, 220 nM, product retention=29.5 min) to provide 2-hydroxy-N-(2-hydroxyethyl)-2-(4-(5-(3-phenyl-4-(trifluoromethyl)isoxazol-5-yl)-1,2,4-oxadiazol-3-yl)phenyl)acetamide (40 mg, 0.078 mmol, 56.4% yield) as a single enantiomer. LCMS=475.2 [M+H]+; 1H NMR (400 MHz, methanol-d4) δ ppm 8.15 (2 H, d, J=8.36 Hz), 7.52-7.73 (7 H, m), 5.14 (1 H, s), 3.64 (2 H, t), 3.38 (2 H, td, J=5.67, 3.63 Hz), 2.15 (1 H, s); HPLC peak RT=8.4 min (Method A).

Workup

  1. customwas purified by prep HPLC (PHENOMENEX® Luna 5u 21×250 mm, gradient elution with Method 1—MeOH/water containing 0.1% trifluoroacetic acid as defined above, 0% B to 100% B over 30 min, 25 mL/min, 220 nM, product retention=29.5 min)

Sources & evidence

ORD record
ord-31e933723f024095ba47c2408a33f571
Source dataset
uspto-grants-2014_09
Patent number
US08835470B2

Reaction notes

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