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

HRID 716834Notes

Reaction equation

HRID 716834 reaction equation
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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
42.5 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-54b2d1ae0ecc424a997a54f71b2379f0
Source dataset
uspto-grants-2015_11
Patent number
US09193687B2

Reaction notes

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