2-Amino-4-methylthiazole → N-(4-methylthiazol-2-yl)-3-(pyridin-3-yloxy)benzamide

HRID 2401495Notes

Reaction equation

HRID 2401495 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([O:7][C:8]2[CH:9]=[C:10]([CH:14]=[CH:15][CH:16]=2)[C:11]([OH:13])=O)[CH:2]=1.[CH3:17][C:18]1[N:19]=[C:20]([NH2:23])[S:21][CH:22]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:17][C:18]1[N:19]=[C:20]([NH:23][C:11](=[O:13])[C:10]2[CH:14]=[CH:15][CH:16]=[C:8]([O:7][C:3]3[CH:2]=[N:1][CH:6]=[CH:5][CH:4]=3)[CH:9]=2)[S:21][CH:22]=1

Participants

7

Reactant 4

HCID 741432-Amino-4-methylthiazoleHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 185485043-(Pyridin-3-yloxy)benzoic acid

Product 1

HCID 51033561N-(4-methylthiazol-2-yl)-3-(pyridin-3-yloxy)benzamideYield 26%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Compound 2 (0.1 g, 0.5 mmol, 1 eq), 4-methylthiazol-2-amine (111 mg, 0.972 mmol, 2.10 eq), 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (371 g, 0.972 mmol, 2.10 eq), and DIEA (170 μL, 0.972 mmol, 2.10 eq) were dissolved in CH2Cl2 (5 mL) and DMF (1 mL) and stirred rt for 48 h. The reaction was diluted with CH2Cl2 and washed with water (1×). The organics were dried (MgSO4), filtered and concentrated in vacuo. Purification by flash chromatography on silica gel afforded 38 mg (26%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.56 (d, J=2.1 Hz, 1H), 8.49 (d, J=4.6 Hz, 1H), 7.94-7.90 (m, 1H), 7.76 (t, J=2.0 Hz, 1H), 7.69 (ddd, J=8.5, 2.7, 1.1 Hz, 1H), 7.62-7.57 (m, 2H), 7.38 (dd, J=8.0, 2.1 Hz, 1H), 6.81 (s, 1H), 2.29 (s, 3H); [M+1]+: 312.1.

Workup

  1. washwashed with water (1×)
  2. dry with materialThe organics were dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customPurification by flash chromatography on silica gel

Sources & evidence

ORD record
ord-60a53221361044ccb04c4304ea54e82c
Source dataset
uspto-grants-2014_08
Patent number
US08796295B2

Reaction notes

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