4-Chloro-6-nitroquinoline → N-[4-(2-Amino-6-methylpyrimidin-4-ylamino)phenyl]-4-(6-nitroquinolin-4-ylamino)benzamide hydrochloride

HRID 1711351Notes

Reaction equation

HRID 1711351 reaction equation
Cl.[NH2:2][C:3]1[CH:26]=[CH:25][C:6]([C:7]([NH:9][C:10]2[CH:15]=[CH:14][C:13]([NH:16][C:17]3[CH:22]=[C:21]([CH3:23])[N:20]=[C:19]([NH2:24])[N:18]=3)=[CH:12][CH:11]=2)=[O:8])=[CH:5][CH:4]=1.[Cl:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[C:35]([N+:38]([O-:40])=[O:39])[CH:36]=2)[N:31]=[CH:30][CH:29]=1>CO.Cl>[ClH:27].[NH2:24][C:19]1[N:18]=[C:17]([NH:16][C:13]2[CH:12]=[CH:11][C:10]([NH:9][C:7](=[O:8])[C:6]3[CH:25]=[CH:26][C:3]([NH:2][C:28]4[C:37]5[C:32](=[CH:33][CH:34]=[C:35]([N+:38]([O-:40])=[O:39])[CH:36]=5)[N:31]=[CH:30][CH:29]=4)=[CH:4][CH:5]=3)=[CH:15][CH:14]=2)[CH:22]=[C:21]([CH3:23])[N:20]=1

Participants

5

Reactant 2

HCID 2872104-Chloro-6-nitroquinoline2×HCID 672000444-Amino-N-[4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl]benzamide hydrochloride2×

Product 1

HCID 24857961N-[4-(2-Amino-6-methylpyrimidin-4-ylamino)phenyl]-4-(6-nitroquinolin-4-ylamino)benzamide hydrochloride

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidCatalyst2×HCID 887MethanolSolvent

Procedure

To a solution of amine E5 (304 mg, 0.82 mmol) in dry MeOH (30 mL) were sequentially added 4-chloro-6-nitroquinoline (F1) (171 mg, 0.82 mmol) and c.HCl (1-2 drops), and the resulting mixture was refluxed for ˜12 h. MS and TLC analysis after this time showed some F1 was still present in the reaction mixture, so further aliquots of E5 (171 mg, 0.82 mmol) and c.HCl (1-2 drops) were added at 12 h and 24 h. Solvent was then removed from the reaction mixture, and the resulting residue dissolved in MeOH, and then re-concentrated under reduced pressure. The residue was subjected to a further MeOH azeotrope cycle, and the resulting residue was then reprecipitated from MeOH:Et2O to afford Cpd. H as an amorphous yellow solid (383 mg, 86%). 1H NMR (400 MHz, DMSO): 2.28 [s, 3H, ArCH3], 6.18 [brs, 1H, ArH], 7.11 [d, J=6.59 Hz, 1H, ArH], 7.65 Hz [d, J=8.52 Hz, 2H, ArH], 7.81 [m, 5H, ArH &ArNH2], 8.17 [d, J=8.52 Hz, 2H, ArH], 8.25 [d, J=9.30 Hz, 1H, ArH], 8.69 [m, 2H, ArH], 9.77 [s, 1H, ArH], 10.42 [s, 1H, ArH], 10.62 [br s, 1H, ArNHAr], 11.20 [v br s, 1H, ArNHAr], 12.63 [v br s, 1H, ArC(O)NH]. LCMS (APCl+): 508 (100%). HPLC: 98.5%.

Workup

  1. customSolvent was then removed from the reaction mixture
  2. dissolutionthe resulting residue dissolved in MeOH
  3. concentrationre-concentrated under reduced pressure
  4. customthe resulting residue was then reprecipitated from MeOH
  5. customEt2O to afford Cpd

Sources & evidence

ORD record
ord-9f669d8d31b04a549b664d4ed963d48b
Source dataset
uspto-grants-2010_09
Patent number
US07790746B2

Reaction notes

Loading…