1-(2-Hydroxyethyl)piperazine → HCID 5330061, compound

HRID 1611517Notes

Reaction equation

HRID 1611517 reaction equation
[OH:1][CH2:2][CH2:3][N:4]1[CH2:9][CH2:8][NH:7][CH2:6][CH2:5]1.[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:26]([C:27]#[N:28])=[CH:25][N:24]=[C:23]2[CH:29]=[C:30]([C:32]3[CH:37]=[CH:36][C:35]([CH:38]=O)=[CH:34][CH:33]=3)[S:31][C:22]=12.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O.C(O)(=O)C>[Cl:10][C:11]1[CH:16]=[C:15]([Cl:17])[C:14]([O:18][CH3:19])=[CH:13][C:12]=1[NH:20][C:21]1[C:26]([C:27]#[N:28])=[CH:25][N:24]=[C:23]2[CH:29]=[C:30]([C:32]3[CH:37]=[CH:36][C:35]([CH2:38][N:7]4[CH2:8][CH2:9][N:4]([CH2:3][CH2:2][OH:1])[CH2:5][CH2:6]4)=[CH:34][CH:33]=3)[S:31][C:22]=12

Participants

7

Reactant 3

HCID 76771-(2-Hydroxyethyl)piperazineHCID 5049666Sodium triacetoxyborohydrideHCID 10343928HCID 10343928, compound

Product 1

HCID 5330061HCID 5330061, compoundYield 35.2%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-(2-Hydroxyethyl)piperazine (104 mg, 0.80 mmol) is added to a suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile (227 mg, 0.50 mmol) in 15 mL of dichloromethane and 1 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (800 mg, 3.8 mmol) is added. After stirring at 0° C. for 1.5 hours, 2 drops of acetic acid are added and the reaction mixture is allowed to warm to room temperature and stirred overnight. The reaction is quenched by the addition of water and then partitioned between aqueous sodium bicarbonate and dichloromethane. The organic layer is dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with 10% methanol in dichloromethane to provide 100 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(4-{[4-(2-hydroxyethyl)piperazin-1-yl]methyl}phenyl)thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 189-190° C.; 1H NMR (DMSO-d6) δ 2.27-2.44 (m, 10H), 3.41-3.50 (m, 4H), 3.85 (s, 3H), 4.36 (s, 1H), 7.37 (s, 1H), 7.40 (d, J=8 Hz, 2H), 7.67 (d, J=8 Hz, 2H), 7.76 (s, 1H), 7.89 (s, 1H), 8.60 (s, 1H), 9.74 (s, 1H); MS 566.3 (M−H)−.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred overnight
  3. customThe reaction is quenched by the addition of water
  4. custompartitioned between aqueous sodium bicarbonate and dichloromethane
  5. dry with materialThe organic layer is dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue is purified by flash column chromatography
  9. washeluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-514b261a70594d62941cf961e605b9b8
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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