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

HRID 716843

반응식

HRID 716843 반응식
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

참가 물질

7

반응물 4

HCID 8471Triethylamine2회HCID 94429TriphosgeneHCID 2157271,4-Benzenediamine, N1,N1-bis(2-chloroethyl)-, hydrochloride (1:?)2회HCID 3804823-(9-Acridinylamino)-5-hydroxymethylaniline

생성물 1

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

시약·촉매·용매 2

HCID 6212Chloroform용매HCID 6228Dimethylformamide용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-ca5eaed26fce4e47936410a774648dad
출처 데이터셋
uspto-grants-2015_11
특허 번호
US09193687B2

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