Nitrogen mustard hydrochloride → HCID 178433636, compound

HRID 2271113Notes

Reaction equation

HRID 2271113 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[C:10]([C:15](=[O:25])[N:16]([C:18]4[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=4)[N:17]=3)=[CH:11][NH:12][C:13]=2[CH3:14])[CH:5]=[CH:6][CH:7]=1.[CH3:26][N:27]([CH2:31][CH2:32]Cl)[CH2:28][CH2:29][Cl:30].Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CCC>[CH2:21]([Cl:24])[Cl:30].[CH3:15][OH:25].[NH3:1].[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([N:16]2[C:15](=[O:25])[C:10]3=[CH:11][NH:12][C:13]([CH3:14])=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([N:1]5[CH2:32][CH2:31][N:27]([CH3:26])[CH2:28][CH2:29]5)[CH:3]=4)[C:9]3=[N:17]2)=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 5935Nitrogen mustard hydrochloride2×HCID 10340Sodium CarbonateHCID 178433638HCID 178433638, compound

Product 2

HCID 21584172Ammonia methanol dichloromethaneHCID 178433636HCID 178433636, compoundYield 23.9%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Procedure

A stirred mixture of 7-(3-aminophenyl)-2-(4-chlorophenyl)-2,5-dihydro-6-methylpyrazolo[4,3-c]pyridin-3-one (0.1997 g, 0.570 mmol), and mechlorethamine hydrochloride (0.1293 g, 0.672 mmol) in anhydrous 1-butanol (4 ml) was heated at reflux under nitrogen for 50 h, adding sodium carbonate (24.7 mg, 0.233 mmol) after 22 h and more mechlorethamine hydrochloride (0.4807 g, 2.50 mmol) after 26 h. The solvent was removed in vacuo and the residue was purified by flash chromatography [silica gel, 5-30% MeOH/CH2Cl2; then silica gel, CH2Cl2-MeOH-NH3 (95:5:0.5 to 93:7:0.7)], to afford 29.6 mg (12%) of the title compound as a yellow solid; mp 191-210° C. (CH2Cl2-EtOAc-hexane); 1H NMR (360 MHz, DMSO-d6) δ2.25 (3H, s), 2.26 (3H, s), 2.50 (4H, m), 3.20 (4H, m), 6.89 (1H, d, J 7.5 Hz), 6.99 (1H, m), 7.05 (1H, s), 7.33 (1H, t, J 7.9 Hz), 7.42 (2H, d, J9.0 Hz), 8.13 (2H, d, J8.9 Hz), 8.54 (1H, s), 12.44 (1H, br s); MS (ES+) m/z 434/436[MH]+, 218[(M+2H)/]+. Anal. found: C, 64.41; H, 5.63; N, 15.44. C24H24ClN5O.0.7H2O requires: C, 64.56; H, 5.73; N, 15.68%.

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 50 h
  3. customThe solvent was removed in vacuo
  4. customthe residue was purified by flash chromatography [silica gel, 5-30% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-ce58032c79f84746bbe6a45cbef4f4d7
Source dataset
uspto-grants-2001_12
Patent number
US06333336B1

Reaction notes

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