Morpholine → HCID 10256060, compound

HRID 1611543Notes

Reaction equation

HRID 1611543 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[CH:7]([C:9]1[CH:14]=[CH:13][C:12]([C:15]2[S:23][C:22]3[C:17](=[N:18][CH:19]=[C:20]([C:38]#[N:39])[C:21]=3[NH:24][C:25]3[CH:30]=[CH:29][C:28]([O:31][C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)=[CH:27][CH:26]=3)[CH:16]=2)=[CH:11][CH:10]=1)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.CN(C)C=O.C(O)(=O)C>[N:1]1([CH2:7][C:9]2[CH:10]=[CH:11][C:12]([C:15]3[S:23][C:22]4[C:17](=[N:18][CH:19]=[C:20]([C:38]#[N:39])[C:21]=4[NH:24][C:25]4[CH:30]=[CH:29][C:28]([O:31][C:32]5[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=5)=[CH:27][CH:26]=4)[CH:16]=3)=[CH:13][CH:14]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

7

Reactant 3

HCID 8083MorpholineHCID 5049666Sodium triacetoxyborohydrideHCID 10343583HCID 10343583, compound

Product 1

HCID 10256060HCID 10256060, compoundYield 33.8%

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Morpholine (51 μL, 0.58 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 8 mL of dichloromethane and 2 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, 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 residue is purified by flash column chromatography eluting with ethyl acetate to provide 79 mg of 2-[4-(morpholin-4-ylmethyl)phenyl]-7-[(4-phenoxyphenyl)amino]thieno[3,2-b]pyridine-6-carbonitrile as white crystals, mp 254-256° C.; 1H NMR (DMSO-d6) δ 2.36 (s, 4H), 3.51 (s, 2H), 3.58 (s, 4H), 7.04-7.18 (m, 5H), 7.34-7.45 (m, 6H), 7.67 (d, J=8 Hz, 2H), 7.86 (s, 1H), 8.59 (s, 1H), 9.58 (s, 1H); MS 519.2 (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 ethyl acetate

Sources & evidence

ORD record
ord-5cdde9a6712a40878ffb2bf414c13bf9
Source dataset
uspto-grants-2006_01
Patent number
US06987116B2

Reaction notes

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