Hydrochloric Acid → 3-[(2,6-Diamino-4-pyrimidinyl)amino]-N-[4-(4-quinolinylamino)-phenyl]benzamide dihydrochloride

HRID 547545Notes

Reaction equation

HRID 547545 reaction equation
[ClH:1].[NH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:26])[C:11]2[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]3[CH:23]=[C:22]([NH2:24])[N:21]=[C:20]([NH2:25])[N:19]=3)[CH:12]=2)=[CH:5][CH:4]=1.[Cl:27][C:28]1[C:37]2[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=2)[N:31]=[CH:30][CH:29]=1.Cl.CO.CCOC(C)=O>CCO.O.CCOC(C)=O.CO>[ClH:27].[ClH:1].[NH2:25][C:20]1[N:19]=[C:18]([NH:17][C:13]2[CH:12]=[C:11]([CH:16]=[CH:15][CH:14]=2)[C:10]([NH:9][C:6]2[CH:7]=[CH:8][C:3]([NH:2][C:28]3[C:37]4[C:32](=[CH:33][CH:34]=[CH:35][CH:36]=4)[N:31]=[CH:30][CH:29]=3)=[CH:4][CH:5]=2)=[O:26])[CH:23]=[C:22]([NH2:24])[N:21]=1

Participants

9

Reactant 4

HCID 313Hydrochloric Acid3×HCID 691404-ChloroquinolineHCID 21584119Ethylacetate methanolHCID 67200187N-(4-Aminophenyl)-3-[(2,6-diamino-4-pyrimidinyl)amino]benzamide hydrochloride

Product 1

HCID 671999893-[(2,6-Diamino-4-pyrimidinyl)amino]-N-[4-(4-quinolinylamino)-phenyl]benzamide dihydrochloride

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 887MethanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
20 °C

Procedure

To a solution of compound B6 (150 mg, 0.37 mmol) in EtOH (15 mL) and H2O (7.5 mL) was added 4-chloroquinoline (73 mg, 0.45 mmol) and stirred until it dissolved, then 2 drops of c.HCl was added. The reaction mixture was refluxed for 20 h, diluted with EtOAc, brought to boil and cool to 20° C. The resulting precipitate was filtered and stirred in aqueous NH3 (20 ml) to convert to free base. This new precipitate was filtered and chromatographed (neutral Al2O3, 0-7% DCM/MeOH) to give pure free base of the product. This was then converted to HCl salt by using 1.25 M HCl in MeOH to give Cpd. FF2 (139 mg, 70%); m.p (MeOH/EtOAc)>300° C. 1H NMR [(CD3)2SO] δ14.25 (br, 1 H, N+H), 12.00 (br, 1 H, N+H), 10.95 (s, 1 H, NH), 10.53 (s, 1 H, NH), 9.93 (s, 1 H, NH), 9.05 (d, J=8.5 Hz, 1 H, ArH), 7.51 (d, J=7.0 Hz, 1 H, ArH), 8.06-8.00 (m, 5 H, ArH), 7.95-7.91 (br m, 2 H, NH2), 7.81 (d d, J=7.6, 1.4 Hz, 1 H, ArH), 7.71 (d, J=7.6 Hz, 1 H, ArH), 7.58 (s, 2 H, NH2), 7.57-7.47 (m, 5 H, ArH), 6.78 (d, J=7.0 Hz, 1 H, ArH), 6.78 (d, J=7.0 Hz, 1 H, ArH), 5.46 (s, 1 H, ArH); HRMS (FAB+) calc. for C26H23N8O (M+1) m/z 463.1995, found 463.1992.

Workup

  1. dissolutiondissolved
  2. temperatureThe reaction mixture was refluxed for 20 h
  3. filtrationThe resulting precipitate was filtered
  4. stirringstirred in aqueous NH3 (20 ml)
  5. filtrationThis new precipitate was filtered
  6. customchromatographed (neutral Al2O3, 0-7% DCM/MeOH)
  7. customto give pure free base of the product
  8. customto give Cpd

Sources & evidence

ORD record
ord-780152633d894a6d80b66feb2435ed7c
Source dataset
uspto-grants-2011_05
Patent number
US07939546B2

Reaction notes

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