Hydrochloric Acid → N-[4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl]-4-(6-(dimethylamino)quinolin-4-ylamino)benzamide hydrochloride

HRID 547535Notes

Reaction equation

HRID 547535 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.CCO.Cl.[Cl:31][C:32]1[C:41]2[C:36](=[CH:37][CH:38]=[C:39]([N:42]([CH3:44])[CH3:43])[CH:40]=2)[N:35]=[CH:34][CH:33]=1>O>[ClH:31].[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:32]4[C:41]5[C:36](=[CH:37][CH:38]=[C:39]([N:42]([CH3:44])[CH3:43])[CH:40]=5)[N:35]=[CH:34][CH:33]=4)=[CH:4][CH:5]=3)=[CH:15][CH:14]=2)[CH:22]=[C:21]([CH3:23])[N:20]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 436172264-chloro-N,N-dimethylquinolin-6-amine2×HCID 672000444-Amino-N-[4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl]benzamide hydrochloride

Product 1

HCID 67200018N-[4-(2-amino-6-methylpyrimidin-4-ylamino)phenyl]-4-(6-(dimethylamino)quinolin-4-ylamino)benzamide hydrochloride

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of amide E5 (228 mg, 0.62 mmol) in 1:2 EtOH:H2O (20 mL) were sequentially added c.HCl (0.17 mL, 5.61 mmol) and 4-chloro-6-dimethylaminoquinoline (03) (140 mg, 0.68 mmol), and the resulting mixture was refluxed for ˜12 h. MS and TLC analysis (eluting with the top phase of a 5:4:1 mixture of n-BuOH:H2O:AcOH) after this time showed some starting material still present in the reaction mixture, thus more 03 (140 mg, 0.68 mmol) was added. After a further few hours refluxing, TLC showed the reaction was complete, and thus solvent was removed under reduced pressure. The residue was crystallized from MeOH:EtOAc to afford Cpd. P as an (extremely fine) amorphous yellow solid (170 mg, 51%). 1H NMR [(CD3)2SO] δ2.28 [s, 3H], 3.15 [s, 6H, ArN(CH3)2], 6.21 [br s, 1 H, ArH], 6.89 [d, J=6.71 Hz, 1 H, ArH], 7.65 [m, 5 H, ArH], 7.82 [m, 4 H, ArH & ArNH2], 7.96 [d, J=9.39 Hz, 1 H, ArH], 8.18 [d, J=8.57 Hz, 2 H, ArH], 8.35 [t, J=12.38, 6.19 Hz, 1 H, ArH], 10.44 [br s, 1 H, ArH], 10.65 [br s, 1 H, ArNHAr], 10.71 [s, 1 H, ArNHAr], 12.75 [br s, 1 H, ArC(O)NH], 14.56 [d, J=4.10 Hz, 1 H, quinolinyl N+H]. LCMS (APCI+): 506 (100%). HPLC: 97.6%.

Workup

  1. washMS and TLC analysis (eluting with the top phase of a 5:4:1 mixture of n-BuOH
  2. additionwas added
  3. temperatureAfter a further few hours refluxing
  4. customthus solvent was removed under reduced pressure
  5. customThe residue was crystallized from MeOH
  6. customEtOAc to afford Cpd

Sources & evidence

ORD record
ord-0b39c8b62f5746b0b06fe90cd36a9d68
Source dataset
uspto-grants-2011_05
Patent number
US07939546B2

Reaction notes

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