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

HRID 1426182Notes

Reaction equation

HRID 1426182 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH:16][C:17]2[S:18][CH:19]=[C:20]([CH2:22][CH2:23][C:24](O)=[O:25])[N:21]=2)=[N:11][CH:12]=[C:13]([Br:15])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.CN(C(F)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.O[NH:52][C:53](=[NH:55])[CH3:54]>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[C:10]([NH:16][C:17]2[S:18][CH:19]=[C:20]([CH2:22][CH2:23][C:24]3[O:25][N:55]=[C:53]([CH3:54])[N:52]=3)[N:21]=2)=[N:11][CH:12]=[C:13]([Br:15])[CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2774761Tetramethylfluoroformamidinium hexafluorophosphateHCID 592256873-(2-(3-(Benzyloxy)-5-bromopyridin-2-ylamino)thiazol-4-yl)propanoic acidHCID 178465666HCID 178465666, compound

Product 1

HCID 592256503-(benzyloxy)-5-bromo-N-(4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-yl)pyridin-2-amineYield 50.5%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of 3-(2-(3-(benzyloxy)-5-bromopyridin-2-ylamino)thiazol-4-yl)propanoic acid (0.200 g, 0.461 mmol), N,N-diisopropylethylamine (0.0882 ml, 0.507 mmol) in DMF (5 mL) at ambient temperature was added N-((dimethylamino)fluoromethylene)-N-methylmethanaminium hexafluorophosphate(V) (0.122 g, 0.461 mmol). The mixture was stirred for 30 minutes at ambient temperature, and then N-hydroxyacetamidine (0.0375 g, 0.507 mmol) was added in one portion. The reaction mixture was heated at 110° C. overnight and then cooled to ambient temperature. Ethyl acetate was added and the organic layer was washed with water. The combined organic layers were dried over Na2SO4, filtered, and concentrated to a residue that was purified on a silica gel column, eluting with 40% EtOAc/Hexanes. The isolated material was recrystallized from EtOAc/Hexanes and dried under high vacuum to afford 3-(benzyloxy)-5-bromo-N-(4-(2-(3-methyl-1,2,4-oxadiazol-5-yl)ethyl)thiazol-2-yl)pyridin-2-amine (0.110 g, 50% yield) as a tan solid. 1H NMR (DMSO-d6) δ 2.30 (s, 3H), 3.05 (t, J=7.6 Hz, 2H), 3.26 (t, J=7.6 Hz, 2H), 5.29 (s, 2H), 6.73 (s, 1H), 7.35 (t, J=7.2 Hz, 1H), 7.42 (t, J=7.2 Hz, 2H), 7.58 (s, 1H), 7.60 (s, 1H), 7.63 (d, J=1.6 Hz, 1H), 7.97 (d, J=2.0 Hz, 1H), 10.32 (s, 1H); Mass Spectrum (apci) 472 (M+H).

Workup

  1. temperatureThe reaction mixture was heated at 110° C. overnight
  2. temperaturecooled to ambient temperature
  3. washthe organic layer was washed with water
  4. dry with materialThe combined organic layers were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated to a residue that
  7. customwas purified on a silica gel column
  8. washeluting with 40% EtOAc/Hexanes
  9. customThe isolated material was recrystallized from EtOAc/Hexanes
  10. customdried under high vacuum

Sources & evidence

ORD record
ord-5b1130525d794d1b87130d24a4b3953f
Source dataset
uspto-grants-2015_01
Patent number
US08933077B2

Reaction notes

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