Dichloromethane → 7-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester

HRID 1108018Notes

Reaction equation

HRID 1108018 reaction equation
[CH3:1][O:2][C:3]([C:5]1[C:6]([Cl:21])=[N:7][C:8]2[CH:9]=[C:10]3[O:20][CH2:19][CH2:18][O:17][C:11]3=[CH:12][C:13]=2[C:14]=1[CH2:15]Cl)=[O:4].C(Cl)Cl.[CH3:25][N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1>O>[CH3:1][O:2][C:3]([C:5]1[C:6]([Cl:21])=[N:7][C:8]2[CH:9]=[C:10]3[O:20][CH2:19][CH2:18][O:17][C:11]3=[CH:12][C:13]=2[C:14]=1[CH2:15][N:29]1[CH2:30][CH2:31][N:26]([CH3:25])[CH2:27][CH2:28]1)=[O:4]

Participants

5

Reactant 3

HCID 6344DichloromethaneHCID 531671-MethylpiperazineHCID 154504607-Chloro-9-chloromethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester2×

Product 1

HCID 154504617-Chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A 4-necked 5-L round-bottom flask is equipped with a mechanical stirrer and 250-mL addition funnel. Under nitrogen, the flask is charged with 7-chloro-9-chloromethyl-2,3-dihydro[1,4]dioxino[2,3-g]quinoline-8-carboxylic acid methyl ester (Intermediate 6, 340 g, 1.04 mol), and methylene chloride (2 L). To the stirred solution is added N-methylpiperazine (237 mL, 2.14 mol) over 10 min. After the addition is complete, the reaction mixture is stirred at ambient temperature for 15 h. The reaction mixture is poured into water (3 L) and the organic layer is separated. The aqueous layer is extracted with methylene chloride (3×2 L). The combined organic layers are washed with brine (2 L), dried over anhydrous sodium sulfate and concentrated in vacuo.. The resultant thick brown slurry is successively treated with methylene chloride (300 mL) and hexane (1.5 L). The mixture is swirled at 0° C. for 30 min. The precipitate is collected on a Buchner funnel, washed with hexane (1 L) and dried in vacuo. at 30° C. yielding 7-chloro-9-(4-methylpiperazin-1-ylmethyl)-2,3-dihydro[1,4]dioxino [2,3-g]quinoline-8-carboxylic acid methyl ester as a yellow powder: mp 143° C. 1H NMR (CDCl3, 200 MHz) d 2.28 (s, 3H), 2.38-2.49 (m, 8H), 3.81 (s, 2H), 3.96 (s, 3H), 4.59 (s, 2H), 4.40 (s, 4H), 7.45 (s, 1H), 7.65 (s, 1H). Elemental analysis: Calculated for C19H22ClN3O4 : C 58.24, H 5.66, N 10.72. Found: C 58.08, H 5.72, N 10.63.

Workup

  1. customA 4-necked 5-L round-bottom flask is equipped with a mechanical stirrer and 250-mL addition funnel
  2. additionAfter the addition
  3. customthe organic layer is separated
  4. extractionThe aqueous layer is extracted with methylene chloride (3×2 L)
  5. washThe combined organic layers are washed with brine (2 L)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. additionThe resultant thick brown slurry is successively treated with methylene chloride (300 mL) and hexane (1.5 L)
  9. waitThe mixture is swirled at 0° C. for 30 min
  10. customThe precipitate is collected on a Buchner funnel
  11. washwashed with hexane (1 L)
  12. customdried in vacuo

Sources & evidence

ORD record
ord-11244de1704c42dfbd112ce9d8eb8807
Source dataset
uspto-grants-2000_05
Patent number
US06063923

Reaction notes

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