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

HRID 716844

Reaction equation

HRID 716844 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.[CH:35]1[C:48]2[C:39](=[N:40][C:41]3[C:46]([C:47]=2[NH:49][C:50]2[CH:55]=[C:54]([CH3:56])[CH:53]=[C:52]([NH2:57])[CH:51]=2)=[CH:45][CH:44]=[CH:43][CH:42]=3)[CH:38]=[CH:37][CH:36]=1>C(Cl)(Cl)Cl.CN(C=O)C.N1C=CC=CC=1>[CH:45]1[C:46]2[C:41](=[N:40][C:39]3[C:48]([C:47]=2[NH:49][C:50]2[CH:51]=[C:52]([NH:57][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:53]=[C:54]([CH3:56])[CH:55]=2)=[CH:35][CH:36]=[CH:37][CH:38]=3)[CH:42]=[CH:43][CH:44]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 2157271,4-Benzenediamine, N1,N1-bis(2-chloroethyl)-, hydrochloride (1:?)HCID 10063333N-acridin-9-yl-5-methylbenzene-1,3-diamine

Product 1

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

Reagents, catalysts & solvents 3

HCID 1049PyridineSolventHCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of N,N-bis(2-chloroethyl)benzene-1,4-diamine hydrochloride (18, 0.918 g, 3.0 mmol) in dry CHCl3 (35 mL) containing Et3N (0.6 mL) was added dropwise a solution of triphosgene (356 mg, 1.2 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 containing crude N-mustard isocyanate 19 was evaporated in vacuo to dryness and the residue was dissolved in dry DMF (5 mL) and then added dropwise into the solution of N-acridin-9-yl-5-methylbenzene-1,3-diamine (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 (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.

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. additionThe filtrate containing crude N-mustard isocyanate 19
  6. customwas evaporated in vacuo to dryness
  7. dissolutionthe residue was dissolved in dry DMF (5 mL)
  8. stirringcontinuously stirred for 24 h
  9. customevaporated in vacuo to dryness
  10. dissolutionThe residue was dissolved in a mixture of CHCl3/MeOH
  11. additioncontaining silica gel (10 g)
  12. customevaporated under reduced pressure to dryness
  13. customchromatographed
  14. additionThe fractions containing the main product
  15. customevaporated in vacuo to dryness

Sources & evidence

ORD record
ord-1d33e095bbf04e00aeb96ee394ca7590
Source dataset
uspto-grants-2015_11
Patent number
US09193687B2

Linked notes

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