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

HRID 1178667노트

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HRID 1178667 반응식
[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

참가 물질

7

반응물 3

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

생성물 1

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

시약·촉매·용매 3

HCID 176Acetic Acid촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-3fe4b6c02fe2459e87a207ef8f5766e2
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07276519B2

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