2-Amino-4-methylthiazole → 3-Fluoro-N-(4-methyl-2-thiazolyl)-5-(5-pyrimidinyloxy)benzamide

HRID 2401498Notes

Reaction equation

HRID 2401498 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][C:12]2[CH:13]=[N:14][CH:15]=[N:16][CH:17]=2)[CH:10]=1)[C:5]([OH:7])=O.[CH3:18][C:19]1[N:20]=[C:21]([NH2:24])[S:22][CH:23]=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>[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([O:11][C:12]2[CH:13]=[N:14][CH:15]=[N:16][CH:17]=2)[CH:10]=1)[C:5]([NH:24][C:21]1[S:22][CH:23]=[C:19]([CH3:18])[N:20]=1)=[O:7]

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 58318861HCID 58318861, compound

Product 1

HCID 509909533-Fluoro-N-(4-methyl-2-thiazolyl)-5-(5-pyrimidinyloxy)benzamideYield 51%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Compound 5 (1.0 g, 4.3 mmol, 1.0 eq), 4-methylthiazol-2-amine (585 mg, 5.12 mmol, 1.20 eq), 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (3.4 g, 8.9 mmol, 2.1 eq), and DIEA (1.56 mL, 8.94 mmol, 2.10 eq) were dissolved in CH2Cl2 (21 mL) and DMF (4.2 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 721 mg (51%) of the title compound as a tan solid: 1H NMR (400 MHz, CDCl3) δ 9.09 (s, 1H), 8.77 (s, 2H), 7.74-7.70 (m, 1H), 7.62 (t, J=1.6 Hz, 1H), 7.43 (dt, J=9.6, 2.3 Hz, 1H), 6.83 (d, J=1.0 Hz, 1H), 2.28 (s, 3H); [M+1]+: 331.0.

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-abe035a5a3ad4f869a7792ddc6856d8f
Source dataset
uspto-grants-2014_08
Patent number
US08796295B2

Reaction notes

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