Morpholine → 7-chloro-N-[4-(4-methylpiperazin-1-yl)-3-(morpholin-4-ylmethyl)phenyl]quinolin-4-amine

HRID 1190872Notes

Reaction equation

HRID 1190872 reaction equation
[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([N:21]4[CH2:26][CH2:25][N:24]([CH3:27])[CH2:23][CH2:22]4)=[C:17]([CH2:19]O)[CH:18]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>CN(C=O)C>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([C:6]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([N:21]4[CH2:22][CH2:23][N:24]([CH3:27])[CH2:25][CH2:26]4)=[C:17]([CH2:19][N:32]4[CH2:37][CH2:36][O:35][CH2:34][CH2:33]4)[CH:18]=3)=[CH:7][CH:8]=[N:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 24386Thionyl ChlorideHCID 67248956{5-[(7-Chloroquinolin-4-yl)amino]-2-(4-methylpiperazin-1-yl)phenyl}methanol

Product 1

HCID 532508047-chloro-N-[4-(4-methylpiperazin-1-yl)-3-(morpholin-4-ylmethyl)phenyl]quinolin-4-amineYield 67%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To {5-[(7-chloroquinolin-4-yl)amino]-2-(4-methylpiperazin-1-yl)phenyl}methanol (0.300 g, 0.78 mmol) in 6 mL of DMF at 0° C. was added thionyl chloride (0.28 mL, 5 eq). The reaction mixture was warmed up to room temperature and stirred for 2 h. The solvent was evaporated. The residue was suspended in 6 mL of DMF and morpholine (1.39 mL, 20 eq) was added at 0° C. The solution was stirred overnight at room temperature, evaporated and the residue was purified by flash chromatography (DCM/MeOH/NH4OH//9/1/0.1) to yield expected compound as a pale yellow solid (238 mg, 67% yield). m/z (ESI) 452.2 [M+H]+;

Workup

  1. customThe solvent was evaporated
  2. stirringThe solution was stirred overnight at room temperature
  3. customevaporated
  4. customthe residue was purified by flash chromatography (DCM/MeOH/NH4OH//9/1/0.1)

Sources & evidence

ORD record
ord-a400356973a7430b8c3bcb5e398ab1b2
Source dataset
uspto-grants-2014_03
Patent number
US08680095B2

Reaction notes

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