Triethylamine → N-[7-(3,5-dimethyl-4-isoxazolyl)-4-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-6-(methyloxy)-3-quinolinyl]tetrahydro-2H-pyran-4-carboxamide

HRID 1043005Notes

Reaction equation

HRID 1043005 reaction equation
[O:1]1[CH2:6][CH2:5][CH:4]([C:7]([OH:9])=O)[CH2:3][CH2:2]1.[CH3:10][C:11]1[C:15]([C:16]2[CH:25]=[C:24]3[C:19]([C:20]([NH:27][CH2:28][C:29]4[S:33][C:32]([CH3:34])=[N:31][C:30]=4[CH3:35])=[C:21]([NH2:26])[CH:22]=[N:23]3)=[CH:18][C:17]=2[O:36][CH3:37])=[C:14]([CH3:38])[O:13][N:12]=1.C(N(CC)CC)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O>[CH3:10][C:11]1[C:15]([C:16]2[CH:25]=[C:24]3[C:19]([C:20]([NH:27][CH2:28][C:29]4[S:33][C:32]([CH3:34])=[N:31][C:30]=4[CH3:35])=[C:21]([NH:26][C:7]([CH:4]4[CH2:3][CH2:2][O:1][CH2:6][CH2:5]4)=[O:9])[CH:22]=[N:23]3)=[CH:18][C:17]=2[O:36][CH3:37])=[C:14]([CH3:38])[O:13][N:12]=1

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 219302Oxane-4-carboxylic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 672075147-(3,5-dimethyl-4-isoxazolyl)-N4-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-6-(methyloxy)-3,4-quinolinediamine3×

Product 1

HCID 70664222N-[7-(3,5-dimethyl-4-isoxazolyl)-4-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-6-(methyloxy)-3-quinolinyl]tetrahydro-2H-pyran-4-carboxamide

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tetrahydro-2H-pyran-4-carboxylic acid (0.381 g, intermediate 69) in DCM (60 ml) were successively added triethylamine (0.41 ml) then HATU (1.115 g) and the resulting mixture was stirred for 20 min room temperature. 7-(3,5-dimethyl-4-isoxazolyl)-N4-[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]-6-(methyloxy)-3,4-quinolinediamine (0.6 g, intermediate 69) was added and the mixture stirred at ambient temperature overnight. The reaction mixture was poured into water and extracted with DCM. The organic phase was washed with a dilute sodium hydroxide solution and then with water. The organic phase was dried over Na2SO4 and concentrated to dryness. The crude residue was purified by flash silica gel chromatography eluting DCM/methanol (99:1 then 95:5) to give the desired product as a beige sticky solid (0.71 g). The solid was triturated with hot diisopropylether to give N-[7-(3,5-dimethyl-4-isoxazolyl)-4-{[(2,4-dimethyl-1,3-thiazol-5-yl)methyl]amino}-6-(methyloxy)-3-quinolinyl]tetrahydro-2H-pyran-4-carboxamide (0.6 g) as cream coloured crystals.

Workup

  1. extractionextracted with DCM
  2. washThe organic phase was washed with a dilute sodium hydroxide solution
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated to dryness
  5. customThe crude residue was purified by flash silica gel chromatography
  6. washeluting DCM/methanol (99:1

Sources & evidence

ORD record
ord-a3026ca89e9e4628b1842e86e9967972
Source dataset
uspto-grants-2013_10
Patent number
US08557984B2

Reaction notes

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