1-Methylpiperazine → HCID 5330073, compound

HRID 1611542Notes

Reaction equation

HRID 1611542 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][NH:5][CH2:4][CH2:3]1.[CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]2[S:24][C:23]3[C:18](=[N:19][CH:20]=[C:21]([C:39]#[N:40])[C:22]=3[NH:25][C:26]3[CH:31]=[CH:30][C:29]([O:32][C:33]4[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=4)=[CH:28][CH:27]=3)[CH:17]=2)=[CH:12][CH:11]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O.C(O)(=O)C>[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([CH2:8][C:10]2[CH:11]=[CH:12][C:13]([C:16]3[S:24][C:23]4[C:18](=[N:19][CH:20]=[C:21]([C:39]#[N:40])[C:22]=4[NH:25][C:26]4[CH:31]=[CH:30][C:29]([O:32][C:33]5[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=5)=[CH:28][CH:27]=4)[CH:17]=3)=[CH:14][CH:15]=2)[CH2:4][CH2:3]1

Participants

7

Reactant 3

HCID 531671-MethylpiperazineHCID 5049666Sodium triacetoxyborohydrideHCID 10343583HCID 10343583, compound

Product 1

HCID 5330073HCID 5330073, compoundYield 57.7%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

1-Methylpiperazine (65 μL, 0.59 mmol) is added to a suspension of 2-(4-formylphenyl)-7-[(4-phenoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile (200 mg, 0.45 mmol) in 4 mL of dichloromethane and 1 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (474 mg, 2.24 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 4 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 to provide 138 mg of 2-[4-(4-methylpiperazin-1-ylmethyl)phenyl]-7-[(4-phenoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 199-201° C.; 1H NMR (DMSO-d6) δ 2.17 (s, 3H), 2.37 (br s, 8H), 3.50 (s, 2H), 7.05-7.18 (m, 5H), 7.35-7.44 (m, 6H), 7.66 (d, J=8 Hz, 2H), 7.86 (s, 1H), 8.59 (s, 1H), 9.58 (s, 1H); MS 532.3 (M+H)+.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 4 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

Sources & evidence

ORD record
ord-98c6390e968e49339c694f8d5dfe98af
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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