N-(4-Bromopentyl)phthalimide → 6-Methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(4-phenylbutoxy) quinoline

HRID 1111391Notes

Reaction equation

HRID 1111391 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([O:24][CH3:25])[C:5]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:6]2[C:11]=1[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12].Br[CH:27]([CH3:42])[CH2:28][CH2:29][CH2:30][N:31]1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41]>CCN(CC)CC>[CH3:25][O:24][C:4]1[C:5]([O:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[C:6]2[C:11](=[C:2]([NH:1][CH:27]([CH3:42])[CH2:28][CH2:29][CH2:30][N:31]3[C:35](=[O:36])[C:34]4=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]4[C:32]3=[O:41])[CH:3]=1)[N:10]=[CH:9][CH:8]=[C:7]2[CH3:12]

Participants

4

Reactant 2

HCID 240534N-(4-Bromopentyl)phthalimide3×HCID 6091458-Amino-6-methoxy-4-methyl-5-(4-phenylbutoxy)quinoline

Product 1

HCID 538673786-Methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(4-phenylbutoxy) quinolineYield 109.7%

Reagents, catalysts & solvents 1

HCID 8471TriethylamineSolvent3×

Procedure

A stirred mixture of 8-amino-6-methoxy-4-methyl-5-(4-phenylbutoxy)quinoline (12.8 g, 0.038 mol) and 4-bromo-1-phthalimidopentane (BPP) (22.6 g, 0.076 mol) was heated at 135°-140° C. while Et3N (7 ml) was added in small portions during 1 hr. After 1.5 h at 135°-140° C., second portions of BPP (11.3 g) and Et3N (3.5 ml) were added and heating was continued for 2 h. Third portions of BPP (11.3 g) and Et3N (3.5 ml) were introduced and heating was continued for another 2 h. The mixture was allowed to cool and thoroughly extracted with Et2O (total, ca. 600 ml). The extract was treated with charcoal and then with saturated ethereal hydrogen chloride (250 ml). The resulting dark red semi-solid mass was separated by decantation and basified with ethereal Et3N. Concentration of the ethereal solution left a brown oil which was dissolved in CHCl3, placed on a silica gel column (200 g) and eluted with CHCl3. The first fractions were combined on the basis of TLC and concentrated to give 23 g of 6-methoxy-4-methyl-8-(1-methyl-4-phthalimidobutylamino)-5-(4-phenylbutoxy) quinoline as an oil which was used without further purification.

Workup

  1. additionwas added in small portions during 1 hr
  2. temperatureheating
  3. waitwas continued for 2 h
  4. temperatureheating
  5. waitwas continued for another 2 h
  6. temperatureto cool
  7. extractionthoroughly extracted with Et2O (total, ca. 600 ml)
  8. additionThe extract was treated with charcoal
  9. customThe resulting dark red semi-solid mass was separated by decantation
  10. waitConcentration of the ethereal solution left a brown oil which
  11. dissolutionwas dissolved in CHCl3
  12. washeluted with CHCl3
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-78b2c9302a3a439fb7f9196a080187f7
Source dataset
uspto-grants-1990_12
Patent number
US04980360

Reaction notes

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