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

HRID 1178667ノート

反応式

HRID 1178667 の反応式
[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

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 176Acetic Acid触媒HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

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)+.

後処理

  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

出典と根拠

ORDレコード
ord-3fe4b6c02fe2459e87a207ef8f5766e2
出典データセット
uspto-grants-2007_10
特許番号
US07276519B2

反応ノート

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