1-Methylpiperazine → HCID 5330058, compound

HRID 1178643Notes

Reaction equation

HRID 1178643 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([O:16][CH3:17])=[CH:11][C:10]=1[NH:18][C:19]1[C:24]([C:25]#[N:26])=[CH:23][N:22]=[C:21]2[CH:27]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([CH:36]=O)=[CH:32][CH:31]=3)[S:29][C:20]=12.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O.C(O)(=O)C>[Cl:8][C:9]1[CH:14]=[C:13]([Cl:15])[C:12]([O:16][CH3:17])=[CH:11][C:10]=1[NH:18][C:19]1[C:24]([C:25]#[N:26])=[CH:23][N:22]=[C:21]2[CH:27]=[C:28]([C:30]3[CH:35]=[CH:34][C:33]([CH2:36][N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)=[CH:32][CH:31]=3)[S:29][C:20]=12

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 10343928HCID 10343928, compound

Product 1

HCID 5330058HCID 5330058, compoundYield 32.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-methylpiperazine (177 μL, 1.6 mmol) is added to a suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile (560 mg, 1.23 mmol) in 12 mL of dichloromethane and 3 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (1.3 g, 6.13 mmol) is added. After stirring at 0° C. for 10 minutes, 3 drops of acetic acid are added and the reaction mixture is allowed to warm to room temperature and stirred for 5.5 hours. The reaction is quenched by the addition of water and then partitioned between saturated aqueous sodium bicarbonate and dichloromethane. The organic layer is washed with water, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane. The fractions containing product are combined and concentrated in vacuo. The residue is washed with diethyl ether to provide 215 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[4-(4-methylpiperazin-1-ylmethyl)phenyl]thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 226–228° C.; 1H NMR (DMSO-d6) δ 2.17 (s, 3H), 2.37 (br s, 8H), 3.49 (s, 2H), 3.85 (s, 3H), 7.37 (s, 1H), 7.40 (d, J=8 Hz, 2H), (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 5.5 hours
  3. customThe reaction is quenched by the addition of water
  4. custompartitioned between saturated aqueous sodium bicarbonate and dichloromethane
  5. washThe organic layer is washed with water
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue is purified by flash column chromatography
  10. washeluting with 5% methanol in dichloromethane
  11. additionThe fractions containing product
  12. concentrationconcentrated in vacuo
  13. washThe residue is washed with diethyl ether

Sources & evidence

ORD record
ord-4a89ff097cb34ff1862643b19a92c8e6
Source dataset
uspto-grants-2007_10
Patent number
US07276519B2

Reaction notes

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