Acetic Acid → 4-(4-methyl-1H-indol-5-ylamino)-5-(5-((4-methylpiperazin-1-yl)methyl)benzofuran-2-yl)nicotinonitrile

HRID 506194Notes

Reaction equation

HRID 506194 reaction equation
[CH:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11]3[CH:12]=[N:13][CH:14]=[C:15]([C:18]=3[NH:19][C:20]3[C:21]([CH3:29])=[C:22]4[C:26](=[CH:27][CH:28]=3)[NH:25][CH:24]=[CH:23]4)[C:16]#[N:17])=[CH:8][C:7]=2[CH:30]=1)=O.[CH3:31][N:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl.CN1C(=O)CCC1>[CH3:29][C:21]1[C:20]([NH:19][C:18]2[C:15]([C:16]#[N:17])=[CH:14][N:13]=[CH:12][C:11]=2[C:9]2[O:10][C:6]3[CH:5]=[CH:4][C:3]([CH2:1][N:35]4[CH2:36][CH2:37][N:32]([CH3:31])[CH2:33][CH2:34]4)=[CH:30][C:7]=3[CH:8]=2)=[CH:28][CH:27]=[C:26]2[C:22]=1[CH:23]=[CH:24][NH:25]2

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 866168355-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile

Product 1

HCID 236272124-(4-methyl-1H-indol-5-ylamino)-5-(5-((4-methylpiperazin-1-yl)methyl)benzofuran-2-yl)nicotinonitrileYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 5-(5-formyl-1-benzofuran-2-yl)-4-[(4-methyl-1H-indol-5-yl)amino]nicotinonitrile (800 mg, 2.04 mmol) in a mixture of CH2Cl2 (40 mL) and NMP (5 mL) at room temperature under nitrogen was added N-methylpiperazine (613 mg, 6.12 mmol) followed by glacial acetic acid (674 mg, 11.22 mmol) and the reaction mixture was stirred at room temperature for 1 h. Sodium triacetoxyborohydride (2.38 g, 11.22 mmol) was added to the reaction mixture and the reaction was stirred at room temperature for 5 h. The reaction mixture was partitioned between CH2Cl2 and aqueous 1N HCl. The aqueous layer was washed with CH2Cl2 and treated with aqueous 1N NaOH whereupon solids precipitated. The solids were collected and dissolved in CH2Cl2. The solution was washed with water thrice and brine, dried over sodium sulfate, and concentrated and the residue was purified by column chromatography (MeOH/CH2Cl2, 6% to 7.5%) to give 560 mg (58%) of 4-[(4-methyl-1H-indol-5-yl)amino]-5-{5-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-2-yl}nicotinonitrile as a yellow solid. HPLC retention time: 5.9 min.(g); melting range: 162-165° C. (decom.); and HRMS: 477.24093.

Workup

  1. stirringthe reaction was stirred at room temperature for 5 h
  2. customThe reaction mixture was partitioned between CH2Cl2 and aqueous 1N HCl
  3. washThe aqueous layer was washed with CH2Cl2
  4. additiontreated with aqueous 1N NaOH whereupon solids
  5. customprecipitated
  6. customThe solids were collected
  7. dissolutiondissolved in CH2Cl2
  8. washThe solution was washed with water thrice and brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customthe residue was purified by column chromatography (MeOH/CH2Cl2, 6% to 7.5%)

Sources & evidence

ORD record
ord-79ee5a46d3674da8a136efee9b1cf7e1
Source dataset
uspto-grants-2010_08
Patent number
US07781591B2

Reaction notes

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