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

HRID 716841Notes

Reaction equation

HRID 716841 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.Cl.[NH2:36][C:37]1[C:38]2[C:43]([N:44]=[C:45]3[C:50]=1[CH:49]=[CH:48][CH:47]=[CH:46]3)=[CH:42][CH:41]=[CH:40][CH:39]=2>C(Cl)(Cl)Cl.CN(C=O)C>[CH:49]1[C:50]2[C:45](=[N:44][C:43]3[C:38]([C:37]=2[NH:36][C:27]([NH:12][C:9]2[CH:10]=[CH:11][C:6]([N:5]([CH2:13][CH2:14][Cl:15])[CH2:4][CH2:3][Cl:2])=[CH:7][CH:8]=2)=[O:33])=[CH:39][CH:40]=[CH:41][CH:42]=3)[CH:46]=[CH:47][CH:48]=1

Participants

7

Reactant 4

HCID 8471Triethylamine2×HCID 86439-Aminoacridine hydrochlorideHCID 94429TriphosgeneHCID 2157271,4-Benzenediamine, N1,N1-bis(2-chloroethyl)-, hydrochloride (1:?)

Product 1

HCID 250172871-Acridin-9-yl-3-{4-[bis(2-chloroethyl)amino]phenyl}urea

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6228DimethylformamideSolvent

Procedure

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 combined filtrate and washings (containing carbamoyl chloride 38) were then added dropwise into a solution of commercially available 9-aminoacridine hydrochloride (248 mg, 1.0 mmol) in dry DMF (10 mL) containing Et3N (0.5 mL) at room temperature. After being stirred for 16 h, the solvent was evaporated under reduced pressure and the residue was dissolved in a mixture of CHCl3/MeOH containing silica gel (5 g) and evaporated in vacuo to dryness. The residue was put on the top of a silica gel column (2×20 cm) using CHCl3/MeOH (50/1v/v) as eluent. The fractions containing the main product were combined and evaporated in vacuo to dryness and residue was recrystallized from acetone to give 1-acridin-9-yl-3-{4-[bis(2-chloroethyl)amino]phenyl}urea (BO-1034); 273 mg (60%); mp 184-186° C.; 1HNMR (DMSO-d6) δ 3.71 (8H, s, 4×CH2), 6.73 (2H, d, J=9.1 Hz, 2×ArH), 7.10-7.13 (2H, m, 2×ArH), 7.28-7.53 (3H, m, 3×ArH), 7.58-7.60 (2H, m, 2×ArH), 7.84 (1H, brs, exchangeable, NH), 8.15 (2H, d, J=9.1 Hz, 2×ArH), 8.22 (1H, m, ArH), 9.37 (1H, brs, exchangeable, NH). Anal. Calcld. for (C24H22Cl2N4O); C, 63.58; H, 4.89; N, 12.36. Found: C, 63.35; H, 5.05; N, 12.09.

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 combined filtrate and washings (containing carbamoyl chloride 38)
  6. stirringAfter being stirred for 16 h
  7. customthe solvent was evaporated under reduced pressure
  8. dissolutionthe residue was dissolved in a mixture of CHCl3/MeOH
  9. additioncontaining silica gel (5 g)
  10. customevaporated in vacuo to dryness
  11. additionThe fractions containing the main product
  12. customevaporated in vacuo to dryness and residue
  13. customwas recrystallized from acetone

Sources & evidence

ORD record
ord-e9400fadb51e46e0b6185e2d4ee5b4de
Source dataset
uspto-grants-2015_11
Patent number
US09193687B2

Reaction notes

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