2-Amino-4-methylthiazole → 4-(methyl(pyridin-3-yl)amino)-N-(4-methylthiazol-2-yl)picolinamide

HRID 1908980Notes

Reaction equation

HRID 1908980 reaction equation
[CH3:1][N:2]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C:9]([OH:11])=O)[CH:4]=1.[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>[CH3:1][N:2]([C:12]1[CH:13]=[N:14][CH:15]=[CH:16][CH:17]=1)[C:3]1[CH:8]=[CH:7][N:6]=[C:5]([C:9]([NH:24][C:21]2[S:22][CH:23]=[C:19]([CH3:18])[N:20]=2)=[O:11])[CH:4]=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 58349312HCID 58349312, compound

Product 1

HCID 867621734-(methyl(pyridin-3-yl)amino)-N-(4-methylthiazol-2-yl)picolinamideYield 26.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Compound 12 (0.1 g, 0.4 mmol, 1 eq), 4-methylthiazol-2-amine (60 mg, 0.53 mmol, 1.2 eq), 2-(1H-7-Azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (348 mg, 0.915 mmol, 2.10 eq), and DIEA (160 μL, 0.915 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 35 mg (25%) of the title compound as a white solid: 1H NMR (400 MHz, CDCl3) δ 8.60 (d, J=2.3 Hz, 1H), 8.56 (dd, J=4.7, 1.1 Hz, 1H), 8.33 (d, J=4.8 Hz, 1H), 7.83 (ddd, J=8.2, 2.4, 1.5 Hz, 1H), 7.55 (dd, J=8.1, 4.7 Hz, 1H), 7.31 (s, 1H), 6.94-6.89 (m, 1H), 8.86 (s, 1H), 3.40 (s, 3H), 2.28 (s, 3H); [M+1]+: 326.2.

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-e5a1a21d7ad346c799ff4af692ed3456
Source dataset
uspto-grants-2013_12
Patent number
US08598345B2

Reaction notes

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