Piperidin-4-ol → HCID 10459908, compound

HRID 1611541Notes

Reaction equation

HRID 1611541 reaction equation
[OH:1][CH: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][CH:2]([OH:1])[CH2:3][CH2:4]4)=[CH:32][CH:31]=3)[S:29][C:20]=12

Participants

7

Reactant 3

HCID 79341Piperidin-4-olHCID 5049666Sodium triacetoxyborohydrideHCID 10343928HCID 10343928, compound

Product 1

HCID 10459908HCID 10459908, compoundYield 50.5%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

4-Hydroxypiperidine (100 mg, 0.99 mmol) is added to a suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile (165 mg, 0.36 mmol) in 5 mL of dichloromethane and 2 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (0.55 g, 2.60 mmol) is added. After stirring at 0° C. for 4 hours, 3 drops of acetic acid are added and the reaction mixture is allowed to warm to room temperature and stirred for 1.5 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 a gradient of ethyl acetate to 5% methanol in ethyl acetate to provide 98 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-{4-[(4-hydroxypiperidin-1-yl)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrile as yellow crystals, mp 149-150° C.; 1H NMR (DMSO-d6) δ 1.35-1.45 (m, 2H), 1.65-1.75 (m, 2H), 2.00-2.10 (m, 2H), 2.62-2.70 (m, 2H), 3.47 (s, 3H), 3.85 (s, 3H), 4.54 (d, J=4 Hz, 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), 8.59 (s, 1H), 9.72 (s, 1H); MS 536.9 (M−H)−.

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 1.5 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 a gradient of ethyl acetate to 5% methanol in ethyl acetate

Sources & evidence

ORD record
ord-e36e44404a4842ad9a844c0d93ade01d
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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