Triethylamine → 1-{4-[Bis(2-chloroethyl)amino]phenyl}-3-(2-methylquinolin-4-yl)urea

HRID 716834

反応式

HRID 716834 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.[NH2:35][C:36]1[C:45]2[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=2)[N:39]=[C:38]([CH3:46])[CH:37]=1>C(Cl)(Cl)Cl.CN(C=O)C>[Cl:2][CH2:3][CH2:4][N:5]([CH2:13][CH2:14][Cl:15])[C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:27]([NH:35][C:36]2[C:45]3[C:40](=[CH:41][CH:42]=[CH:43][CH:44]=3)[N:39]=[C:38]([CH3:46])[CH:37]=2)=[O:33])=[CH:8][CH:7]=1

参加物

7

反応物 4

HCID 8471Triethylamine2 回HCID 811164-Amino-2-methylquinolineHCID 94429TriphosgeneHCID 2157271,4-Benzenediamine, N1,N1-bis(2-chloroethyl)-, hydrochloride (1:?)

生成物 1

HCID 250183111-{4-[Bis(2-chloroethyl)amino]phenyl}-3-(2-methylquinolin-4-yl)urea

試薬・触媒・溶媒 2

HCID 6212Chloroform溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
42.5 °C

実験手順

To a solution of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (18, 0.612 g, 2.0 mmol) in dry CHCl3 (35 mL) containing Et3N (0.4 mL) was added dropwise a solution of triphosgene (231 mg, 0.8 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 then added dropwise into a solution of commercially available 4-amino-2-methylquinoline (0.177 g, 2.0 mmol) in dry DMF (15 mL) containing Et3N (0.5 mL) at 0° C. After being stirred at room temperature for 3 h, the reaction mixture was heated at 40-45° C. for 16 h and then evaporated in vacuo to dryness. The residue was dissolved in a mixture of CHCl3/MeOH, mixed silica gel (10 g) and then evaporated in vacuo to dryness. The residue was put on the top of a silica gel column (2×30 cm) and chromatographed using CHCl3/MeOH (100:2 v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness and the residue was recrystallized from acetone to give 1-{4-[bis(2-chloroethyl)amino]phenyl}-3-(2-methylquinolin-4-yl)urea (BO-1038); 187 mg (40.1%); mp 128-129° C.; 1H NMR (CHCl3-d6) δ 2.63 (3H, s, Me), 3.57 (4H, t, J=6.6 Hz, 2×CH2), 3.66 (4H t, J=6.6 Hz, 2×CH2), 6.56 (2H, d, J=7.9 Hz, 2×ArH), 7.12-7.14 (1H, m, ArH), 7.21 (2H, d, J=8.8 Hz, 2×ArH), 7.26 (1H, s, ArH), 7.44-7.56 (2H, m, 2×ArH), 7.92 (2H, d, J=8.5 Hz, 2×ArH), 8.14 (1H, s, ArH), 8.40 (1H, brs, exchangeable, NH). Anal. Calcd. for (C21H22Cl2N4O: C, 57.94; H, 5.56; N, 12.87. Found: C, 58.27; H, 5.56; N, 12.6.

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 at room temperature for 3 h
  6. customevaporated in vacuo to dryness
  7. dissolutionThe residue was dissolved in a mixture of CHCl3/MeOH
  8. additionmixed silica gel (10 g)
  9. customevaporated in vacuo to dryness
  10. customchromatographed
  11. additionThe fractions containing the main product
  12. customevaporated in vacuo to dryness
  13. customthe residue was recrystallized from acetone

出典と根拠

ORDレコード
ord-54b2d1ae0ecc424a997a54f71b2379f0
出典データセット
uspto-grants-2015_11
特許番号
US09193687B2

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