Methane → 1-[3-(Acridin-9-ylamino)-5-methylphenyl]-3-{4-[bis(2-chloroethyl)amino]phenyl}urea

HRID 1514806

Reaktionsgleichung

Reaktionsgleichung von HRID 1514806
Cl.Cl.[Cl:3][CH2:4][CH2:5][N:6]([CH2:14][CH2:15][Cl:16])[C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][CH:8]=1.C.O=C(Cl)[O:20][C:21](Cl)(Cl)Cl.[CH:26]1[C:39]2[C:30](=[N:31][C:32]3[C:37]([C:38]=2[NH:40][C:41]2[CH:46]=[C:45]([CH3:47])[CH:44]=[C:43]([NH2:48])[CH:42]=2)=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH:29]=[CH:28][CH:27]=1>O1CCOCC1.CN(C=O)C.N1C=CC=CC=1>[CH:36]1[C:37]2[C:32](=[N:31][C:30]3[C:39]([C:38]=2[NH:40][C:41]2[CH:42]=[C:43]([NH:48][C:21]([NH:13][C:10]4[CH:11]=[CH:12][C:7]([N:6]([CH2:14][CH2:15][Cl:16])[CH2:5][CH2:4][Cl:3])=[CH:8][CH:9]=4)=[O:20])[CH:44]=[C:45]([CH3:47])[CH:46]=2)=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:33]=[CH:34][CH:35]=1

Komponenten

8

Edukt 4

HCID 297MethaneHCID 10426DiphosgeneHCID 10063333N-acridin-9-yl-5-methylbenzene-1,3-diamineHCID 21276262N1,N1-bis(2-chloroethyl)benzene-1,4-diamine dihydrochloride

Produkt 1

HCID 250198561-[3-(Acridin-9-ylamino)-5-methylphenyl]-3-{4-[bis(2-chloroethyl)amino]phenyl}urea

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1049PyridineLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
92.5 °C

Versuchsvorschrift

To a suspension of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (37) (0.918 g, 3.0 mmol) and charcoal (20 mg) in dry dioxane (30 mL) was added diphosgene (0.494 g, 2.5 mmol) and then heated at 90-95° C. for 5 h. The mixture was filtered through a pad of Celite and the filtrate containing crude N-mustard isocyanate 39 was added dropwise into the solution of N-acridin-9-yl-5-methylbenzene-1,3-diamine 33 (0.517 g, 1.7 mmol) in dry DMF (25 mL) containing pyridine (2 mL) at −10° C. The reaction mixture was allowed to cool down to room temperature and continuously stirred for 24 h and then evaporated in vacuo to dryness. The residue was dissolved in a mixture of CHCl3/MeOH containing silica gel (10 g) and evaporated under reduced pressure to dryness. The residue was put on the top of a silica gel column (4×30 cm) and chromatographed by using CHCl3/MeOH (100:3 v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness to give 1-[3-(acridin-9-ylamino)-5-methylphenyl]-3-{4-[bis(2-chloroethyl)amino]phenyl}urea (18, BO-1079), 0.375 g (39%); mp 280-285° C.; 1H NMR (DMSO-d6) δ 2.26 (3H, s, Me), 3.68 (8H, s, 4×CH2), 6.68 (2H, d, J=9.0 Hz, ArH) 6.75-6.89 (1H, m, ArH), 7.19-7.32 (3H, m, ArH), 7.40-7.62 (3H, m, ArH), 7.93-8.14 (4H, m, ArH), 8.29 (2H, d, J=9.0 Hz, ArH), 8.94 (1H, brs, exchangeable, NH), 9.37 (1H, brs, exchangeable, NH), 11.51 (1H, brs, exchangeable, NH). Anal. Calcld. for (C31H29C12N5.0.3 H2O): C, 60.88; H, 6.11; N, 11.45. Found: C, 61.08; H, 6.18; N, 11.32.

Aufarbeitung

  1. filtrationThe mixture was filtered through a pad of Celite
  2. additionthe filtrate containing crude N-mustard isocyanate 39
  3. temperatureto cool down to room temperature
  4. customevaporated in vacuo to dryness
  5. dissolutionThe residue was dissolved in a mixture of CHCl3/MeOH
  6. additioncontaining silica gel (10 g)
  7. customevaporated under reduced pressure to dryness
  8. customchromatographed
  9. additionThe fractions containing the main product
  10. customevaporated in vacuo to dryness

Quellen und Nachweise

ORD-Eintrag
ord-e5ed105ce12649228bddf0606704dfee
Quelldatensatz
uspto-grants-2012_07
Patentnummer
US08222297B2

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