Diisopropylethylamine → 7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-nitro-N-((tetrahydro-2H-pyran-4-yl)methyl)quinolin-4-amine

HRID 81984Notes

Reaction equation

HRID 81984 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].CCN(C(C)C)C(C)C.[O:33]1[CH2:38][CH2:37][CH:36]([CH2:39][NH2:40])[CH2:35][CH2:34]1>CN1C(=O)CCC1.O>[CH3:20][C:15]1[C:14]([C:8]2[CH:7]=[C:6]3[C:11]([C:2]([NH:40][CH2:39][CH:36]4[CH2:37][CH2:38][O:33][CH2:34][CH2:35]4)=[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 27732104-AminomethyltetrahydropyranHCID 574655804-(4-Chloro-6-methoxy-3-nitroquinolin-7-yl)-3,5-dimethylisoxazole

Product 1

HCID 709799137-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-nitro-N-((tetrahydro-2H-pyran-4-yl)methyl)quinolin-4-amineYield 93%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

4-Chloro-7-(3,5-dimethyl-4-isoxazolyl)-6-(methyloxy)-3-nitroquinoline (for a preparation see Intermediate 8) (1.06 g, 3.18 mmol) was dissolved in NMP (5 ml), then DIPEA (0.56 ml, 3.18 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (0.75 g, 6.51 mmol) were added at room temperature. The reaction mixture immediately changed colour and within 5 minutes, a thick yellow precipitate was formed. The mixture was stirred for 20 min, then diluted with water (30 ml) and stirred for 10 min. The precipitate was collected by filtration and washed with water (2×20 ml), then dried in vacuo to give 7-(3,5-dimethylisoxazol-4-yl)-6-methoxy-3-nitro-N-((tetrahydro-2H-pyran-4-yl)methyl)quinolin-4-amine (1.22 g, 2.96 mmol, 93% yield) as a bright yellow solid. LCMS (formate) Rt 0.88 min, MH+ 413

Workup

  1. customa thick yellow precipitate was formed
  2. stirringstirred for 10 min
  3. filtrationThe precipitate was collected by filtration
  4. washwashed with water (2×20 ml)
  5. customdried in vacuo

Sources & evidence

ORD record
ord-fb5a97c6c94e445e8cfc6bbbf1d1b42d
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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