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

HRID 716843

反応式

HRID 716843 の反応式
Cl.[Cl:2][CH2:3][CH2:4][N:5]([CH2:13][CH2:14][Cl:15])[C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.CCN(CC)CC.ClC(Cl)(O[C:27](=[O:33])OC(Cl)(Cl)Cl)Cl.[CH:35]1[C:48]2[C:39](=[N:40][C:41]3[C:46]([C:47]=2[NH:49][C:50]2[CH:51]=[C:52]([CH:54]=[C:55]([CH2:57][OH:58])[CH:56]=2)[NH2:53])=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH:38]=[CH:37][CH:36]=1>C(Cl)(Cl)Cl.CN(C=O)C>[CH:35]1[C:48]2[C:39](=[N:40][C:41]3[C:46]([C:47]=2[NH:49][C:50]2[CH:51]=[C:52]([NH:53][C:27]([NH:12][C:9]4[CH:10]=[CH:11][C:6]([N:5]([CH2:13][CH2:14][Cl:15])[CH2:4][CH2:3][Cl:2])=[CH:7][CH:8]=4)=[O:33])[CH:54]=[C:55]([CH2:57][OH:58])[CH:56]=2)=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH:38]=[CH:37][CH:36]=1

参加物

7

反応物 4

HCID 8471Triethylamine2 回HCID 94429TriphosgeneHCID 2157271,4-Benzenediamine, N1,N1-bis(2-chloroethyl)-, hydrochloride (1:?)2 回HCID 3804823-(9-Acridinylamino)-5-hydroxymethylaniline

生成物 1

HCID 250198541-[3-(Acridin-9-ylamino)-5-hydroxymethylphenyl]-3-{4-[bis(2-chloroethyl)amino]phenyl}urea

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (18, 0.306 g, 1.0 mmol) in dry CHCl3 (35 mL) containing Et3N (0.2 mL) was added dropwise a solution of triphosgene (115 mg, 0.4 mmol.) in an ice bath with vigorous stirring for 30 min. The reaction mixture was evaporated and the residue diluted with THF (20 mL), filtered through a pad of Celite, washed with THF (5 mL). The filtrate and washings were combined and was added dropwise into a solution of 3-(acridin-9-yl)amino-5-hydroxymethylaniline (6, AHMA)18 (0.351 g, 1.0 mmol) in dry DMF (10 mL) containing Et3N (0.5 mL) at 0° C. After being stirred for 18 h, the reaction mixture was evaporated in vacuo to dryness and the residue was dissolved in a mixture of CHCl3/MeOH, mixed with silica gel (5 gm) and evaporated in vacuo to dryness. The residue was put on the top of a silica gel column (2×20 cm) and chromatographed using CHCl3/MeOH (100:5 v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness and residue was recrystallized from CHCl3/MeOH to give 1-[3-(acridin-9-ylamino)-5-hydroxymethylphenyl]-3-{4-[bis(2-chloroethyl)amino]phenyl}urea (BO-1037), 205 mg (35%); mp 173-175° C.; 1H NMR (DMSO-d6) δ 3.67 (8H, m, 4×CH2), 4.41 (2H, d, J=6.0 Hz, CH2), 5.14 (1H, t, J=6.0 Hz, exchangeable, OH), 6.37 (1H, s, ArH), 6.68 (2H, d, J=9.1 Hz, 2×ArH,), 6.81 (1H, s, ArH), 7.01 (1H, s, ArH), 7.05-7.19 (1H, m, ArH), 7.24 (2H, d, J=9.1 Hz, 2×ArH), 7.55 (4H, m, 4×ArH) 8.05 (2H, m, 2×ArH), 8.25 (1H, m, ArH) 8.46 (1H, m, ArH), 10.48 (1H, brs, exchangeable, NH). Anal. Calcd. for (C31H29Cl2N5O2): C, 63.81; H, 5.18; N, 12.00. Found: C, 64.07; H, 5.26; N, 11.87.

後処理

  1. customThe reaction mixture was evaporated
  2. additionthe residue diluted with THF (20 mL)
  3. filtrationfiltered through a pad of Celite
  4. washwashed with THF (5 mL)
  5. stirringAfter being stirred for 18 h
  6. customthe reaction mixture was evaporated in vacuo to dryness
  7. dissolutionthe residue was dissolved in a mixture of CHCl3/MeOH
  8. additionmixed with silica gel (5 gm)
  9. customevaporated in vacuo to dryness
  10. customchromatographed
  11. additionThe fractions containing the main product
  12. customevaporated in vacuo to dryness and residue
  13. customwas recrystallized from CHCl3/MeOH

出典と根拠

ORDレコード
ord-ca5eaed26fce4e47936410a774648dad
出典データセット
uspto-grants-2015_11
特許番号
US09193687B2

関連ノート

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