Diisopropylethylamine → 7-(3,5-Dimethylisoxazol-4-yl)-6-methoxy-N-(1-(1-methyl-1H-pyrazol-4-yl)ethyl)-3-nitroquinolin-4-amine

HRID 81991Notes

Reaction equation

HRID 81991 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[N+:21]([O-:23])=[O:22].[CH3:24][N:25]1[CH:29]=[C:28]([CH:30]([NH2:32])[CH3:31])[CH:27]=[N:26]1.CCN(C(C)C)C(C)C>CN1C(=O)CCC1.O>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:32][CH:30]([C:28]4[CH:27]=[N:26][N:25]([CH3:24])[CH:29]=4)[CH3:31])=[C:3]([N+:21]([O-: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

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 230057821-(1-methyl-1H-pyrazol-4-yl)ethan-1-amineHCID 574655804-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole2×

Product 1

HCID 709800257-(3,5-Dimethylisoxazol-4-yl)-6-methoxy-N-(1-(1-methyl-1H-pyrazol-4-yl)ethyl)-3-nitroquinolin-4-amineYield 83%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole (200 mg, 0.599 mmol, for preparation see Intermediate 8) and [1-(1-methyl-1H-pyrazol-4-yl)ethyl]amine (113 mg, 0.9 mmol) were heated in a mixture of DIPEA (0.324 ml, 1.858 mmol) and NMP (15 ml) at 120° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with water (300 ml) and extracted with EtOAc (2×200 ml). The combined organic phase was washed with water (300 ml) and brine (200 ml), dried with sodium sulphate and evaporated. The resulting gum was dissolved in DCM (3 ml) loaded onto a 100 g silica cartridge and eluted with 2M methanolic ammonia/DCM (0-12%). The product-containing fractions were evaporated in vacuo to give 7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-N-(1-(1-methyl-1H-pyrazol-4-yl)ethyl)-3-nitroquinolin-4-amine (0.21 g, 0.497 mmol, 83% yield) which was used in the subsequent step without further purification. LCMS (formate) Rt 0.87 min, MH+ 423.

Workup

  1. extractionextracted with EtOAc (2×200 ml)
  2. washThe combined organic phase was washed with water (300 ml) and brine (200 ml)
  3. dry with materialdried with sodium sulphate
  4. customevaporated
  5. dissolutionThe resulting gum was dissolved in DCM (3 ml)
  6. washeluted with 2M methanolic ammonia/DCM (0-12%)
  7. customThe product-containing fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-1983b6fd8c534a8ab0918089d9c64591
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

Loading…