Diisopropylethylamine → N-(5-bromo-3-phenoxypyridin-2-yl)-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-amine

HRID 335195Notes

Reaction equation

HRID 335195 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]([OH:18])=O)[N:13]=2)=[N:6][CH:7]=1.CCN(C(C)C)C(C)C.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O[NH:51][C:52](=[NH:54])[CH3:53]>CN(C=O)C.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([O:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:5]([NH:8][C:9]2[S:10][CH:11]=[C:12]([CH2:14][CH2:15][C:16]3[O:18][N:54]=[C:52]([CH3:53])[N:51]=3)[N:13]=2)=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 577426713-(2-(5-Bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)propanoic acidHCID 178465666HCID 178465666, compound

Product 1

HCID 57742768N-(5-bromo-3-phenoxypyridin-2-yl)-4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-amineYield 61.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)propanoic acid (0.100 g, 0.238 mmol), DIEA (0.0456 mL, 0.262 mmol) in 5 mL DMF at ambient temperature was added N-((dimethylamino)fluoromethylene)-N-methylmethanaminium hexafluorophosphate(V) (0.0628 g, 0.238 mmol). The mixture was stirred for 30 minutes at ambient temperature and then N-hydroxyacetamidine (0.0194 g, 0.262 mmol) was added in one portion and the reaction was heated at 110° C. overnight. The reaction was then cooled to ambient temperature and EtOAc was added and the organic layer washed with water (2×10 mL), dried over Na2SO4 and concentrated to a residue that was purified on silica gel eluting with 25% EtOAc/Hexanes to give 5 the title compound (0.067 g, 61.4% yield). 1H NMR (d6 DMSO) δ 2.29 (s, 3H), 3.04 (t, 7.6 Hz, 2H), 3.26 (t, J=7.6 Hz, 2H), 6.74 (s, 1H), 7.11 (d, J=7.8 Hz, 2H), 7.21 (t, J=7.3 Hz, 1H), 7.40 (d, J=2.0 Hz, 1H), 7.44 (t, J=8.0 Hz, 2H), 8.22 (d, J=2.0 Hz, 1H), 11.00 (s, 1H).

Workup

  1. temperaturethe reaction was heated at 110° C. overnight
  2. temperatureThe reaction was then cooled to ambient temperature
  3. washthe organic layer washed with water (2×10 mL)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to a residue that
  6. customwas purified on silica gel eluting with 25% EtOAc/Hexanes

Sources & evidence

ORD record
ord-ab447d4607c04db296cbb7bd7ee450b8
Source dataset
uspto-grants-2014_11
Patent number
US08883828B2

Reaction notes

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