Morpholine → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(morpholin-4-ylmethyl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile

HRID 1611540Notes

Reaction equation

HRID 1611540 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([O:15][CH3:16])=[CH:10][C:9]=1[NH:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]2[CH:26]=[C:27]([C:29]3[CH:33]=[C:32]([CH:34]=O)[S:31][CH:30]=3)[S:28][C:19]=12.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O.C(O)(=O)C>[Cl:7][C:8]1[CH:13]=[C:12]([Cl:14])[C:11]([O:15][CH3:16])=[CH:10][C:9]=1[NH:17][C:18]1[C:23]([C:24]#[N:25])=[CH:22][N:21]=[C:20]2[CH:26]=[C:27]([C:29]3[CH:33]=[C:32]([CH2:34][N:1]4[CH2:6][CH2:5][O:4][CH2:3][CH2:2]4)[S:31][CH:30]=3)[S:28][C:19]=12

Participants

7

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 103442217-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile

Product 1

HCID 100072107-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[5-(morpholin-4-ylmethyl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrileYield 73.9%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Morpholine (50 μL, 0.57 mmol) is added to a suspension of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(5-formylthien-3-yl)thieno[3,2-b]pyridine-6-carbonitrile (200 mg, 0.43 mmol) in 4 mL of dichloromethane and 1 mL of N,N-dimethylformamide. The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (460 mg, 2.17 mmol) is added. After stirring at 0° C. for 10 minutes, 2 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 crude residue is purified by flash column chromatography eluting with 5% methanol in dichloromethane to provide 169 mg of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[5-(morpholin-4-ylmethyl)thien-3-yl]thieno[3,2-b]pyridine-6-carbonitrile as a white solid, mp 209-212° C.; MS 531.0 (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 crude residue is purified by flash column chromatography
  10. washeluting with 5% methanol in dichloromethane

Sources & evidence

ORD record
ord-5ff59fa91c864d4c899a3c9974d8fb46
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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