3-Amino-5-methylisoxazole → 2-{2-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-N-(5-methyl-isoxazol-3-yl)-acetamide

HRID 1046938Notes

Reaction equation

HRID 1046938 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[CH:23]=[CH:22][CH:21]=[CH:20][C:14]=3[O:15][CH2:16][C:17](O)=[O:18])[N:10]([C:24](=[O:34])[C:25]3[C:30]([F:31])=[CH:29][C:28]([F:32])=[CH:27][C:26]=3[F:33])[N:9]=2)=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:68][C:69]1[O:73][N:72]=[C:71]([NH2:74])[CH:70]=1>CN(C=O)C>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][CH:11]([C:13]3[CH:23]=[CH:22][CH:21]=[CH:20][C:14]=3[O:15][CH2:16][C:17]([NH:74][C:71]3[CH:70]=[C:69]([CH3:68])[O:73][N:72]=3)=[O:18])[N:10]([C:24](=[O:34])[C:25]3[C:30]([F:31])=[CH:29][C:28]([F:32])=[CH:27][C:26]=3[F:33])[N:9]=2)=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 661723-Amino-5-methylisoxazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67278887{2-[5-(4-Fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-acetic acid

Product 1

HCID 580257502-{2-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-N-(5-methyl-isoxazol-3-yl)-acetamide

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of {2-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-acetic acid (0.031 mmol) in DMF (1 mL) is added DIEA (0.058 mmol), HATU (0.058 mmol) and 5-methyl-isoxazol-3-ylamine (0.058 mmol). The reaction mixture is stirred for 12 hours. The mixture is purified by preparative LC/MS (20-100% MeCN/H2O) to give 2-{2-[5-(4-fluoro-phenyl)-3-(2,4,6-trifluoro-benzoyl)-2,3-dihydro-[1,3,4]thiadiazol-2-yl]-phenoxy}-N-(5-methyl-isoxazol-3-yl)-acetamide: 1H NMR (400 MHz, CDCl3) δ 7.55-7.51 (m, 3H), 7.35-7.26 (m, 2H), 7.05-6.96 (m, 3H), 6.85 (d, J=8 Hz, 1H), 6.69 (t, J=7.6 Hz, 2H), 6.56 (s, 1H), 4.72 (s, 2H), 2.33 (s, 3H); LC/MS (ES+): 571.1 (M+1)+.

Workup

  1. customThe mixture is purified by preparative LC/MS (20-100% MeCN/H2O)

Sources & evidence

ORD record
ord-6a2dd529cca745dc8d0cb46de06f645d
Source dataset
uspto-grants-2013_10
Patent number
US08569345B2

Reaction notes

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