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

HRID 1514806ノート

反応式

HRID 1514806 の反応式
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

参加物

8

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 6228Dimethylformamide溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
92.5 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-e5ed105ce12649228bddf0606704dfee
出典データセット
uspto-grants-2012_07
特許番号
US08222297B2

反応ノート

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