Diisopropylethylamine → 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-phenylethyl]amino}-3-quinolinecarboxamide

HRID 81980Notes

Reaction equation

HRID 81980 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:14]3[C:15]([CH3:20])=[N:16][O:17][C:18]=3[CH3:19])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][C:3]=1[C:21]([NH2:23])=[O:22].CCN(C(C)C)C(C)C.[C:33]1([C@H:39]([NH2:41])[CH3:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>CN1C(=O)CCC1.O.C(Cl)Cl>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:41][C@@H:39]([C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)[CH3:40])=[C:3]([C:21]([NH2:23])=[O:22])[CH:4]=[N:5]3)=[CH:10][C:9]=2[O:12][CH3:13])=[C:18]([CH3:19])[O:17][N:16]=1

Participants

7

Reactant 3

HCID 81531DiisopropylethylamineHCID 6431891-Phenethylamine, (+)-HCID 574655814-Chloro-7-(3,5-dimethylisoxazol-4-yl)-6-methoxyquinoline-3-carboxamide

Product 1

HCID 709800047-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-phenylethyl]amino}-3-quinolinecarboxamideYield 84%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

4-Chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-3-quinolinecarboxamide (for a preparation see Intermediate 9) (3.33 g, 10.04 mmol) was dissolved in NMP (10 ml) and DIPEA (1.8 ml, 10 mmol) and [(1R)-1-phenylethyl]amine (1.58 g, 13.05 mmol) were added, then the solution was heated at 120° C. for 18 h, then cooled to room temperature, diluted with water (100 ml) and extracted with EtOAc (2×100 ml). The organic layer was washed with water (2×100 ml), dried with sodium sulphate and evaporated in vacuo to give a brown gum. This was dissolved in DCM 20 ml) and loaded onto a 100 g silica cartridge, then eluted with MeOH/DCM (0-10%) and product-containing fractions evaporated in vacuo to give 7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-4-{[(1R)-1-phenylethyl]amino}-3-quinolinecarboxamide (3.5 g, 8.40 mmol, 84% yield) as a beige solid. LCMS (formate) Rt 0.84 min, MH+ 417

Workup

  1. temperaturecooled to room temperature
  2. extractionextracted with EtOAc (2×100 ml)
  3. washThe organic layer was washed with water (2×100 ml)
  4. dry with materialdried with sodium sulphate
  5. customevaporated in vacuo
  6. customto give a brown gum
  7. washeluted with MeOH/DCM (0-10%)
  8. additionproduct-containing fractions
  9. customevaporated in vacuo

Sources & evidence

ORD record
ord-ff2a7ee594c44c82b5242953b6a886f6
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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