Acetic Acid → 4-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[4-(morpholin-4-ylmethyl)phenyl]thieno[2,3-b]pyridine-5-carbonitrile

HRID 1611528ノート

反応式

HRID 1611528 の反応式
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[S:20][C:21]([C:23]3[CH:28]=[CH:27][C:26]([CH:29]=O)=[CH:25][CH:24]=3)=[CH:22][C:13]=12.[NH:31]1[CH2:36][CH2:35][O:34][CH2:33][CH2:32]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>CN(C)C=O.ClCCl>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH3:10])=[CH:4][C:3]=1[NH:11][C:12]1[C:17]([C:18]#[N:19])=[CH:16][N:15]=[C:14]2[S:20][C:21]([C:23]3[CH:28]=[CH:27][C:26]([CH2:29][N:31]4[CH2:36][CH2:35][O:34][CH2:33][CH2:32]4)=[CH:25][CH:24]=3)=[CH:22][C:13]=12

参加物

7

反応物 4

HCID 176Acetic AcidHCID 8083Morpholine2 回HCID 5049666Sodium triacetoxyborohydride2 回HCID 112248044-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[2,3-b]pyridine-5-carbonitrile

生成物 1

HCID 53304144-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-[4-(morpholin-4-ylmethyl)phenyl]thieno[2,3-b]pyridine-5-carbonitrile収率 68.2%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

A suspension of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[2,3-b]pyridine-5-carbonitrile (0.1 g, 0.24 mmol) in 1 mL of N,N-dimethylformamide and 4 mL of dichloromethane is prepared. To the mixture is added morpholine (0.03 mL, 0.32 mmol). The reaction mixture is cooled to 0° C. and sodium triacetoxyborohydride (0.26 g, 1.2 mmol) is added. After stirring at 0° C. for 30 minutes a drop of acetic acid is added and the mixture is stirred at 0° C. for an additional 4 hours. Additional morpholine (0.01 mL, 0.1 mmol) and sodium triacetoxyborohydride are added and the reaction mixture is allowed to warm to room temperature and stirred overnight. The resultant light brown solution is partitioned between dichloromethane and water. The organic layer is washed with saturated aqueous sodium chloride and water, dried over magnesium sulfate, filtered and concentrated in vacuo. The resulting residue is triturated with acetone and water to provide 86 mg of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-2-[4-(morpholin-4-ylmethyl)phenyl]thieno[2,3-b]pyridine-5-carbonitrile as a white solid, mp 106-108° C.; 1H NMR (DMSO-d6) δ 2.38 (br s, 4H), 3.51 (br s, 2H), 3.59 (br s, 4H), 3.86 (s, 3H), 7.40 (s, 1H), 7.46 (d, J=8.0 Hz, 2H), 7.67 (d, J=8.0 Hz, 2H), 7.77 (s, 1H), 8.19 (s, 1H), 8.42 (s, 1H), 9.80 (s, 1H); MS 525.0 (M+H)+.

後処理

  1. customis prepared
  2. additionis added
  3. temperatureto warm to room temperature
  4. stirringstirred overnight
  5. customThe resultant light brown solution is partitioned between dichloromethane and water
  6. washThe organic layer is washed with saturated aqueous sodium chloride and water
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue is triturated with acetone and water

出典と根拠

ORDレコード
ord-50971320e0514185a485593719cde323
出典データセット
uspto-grants-2006_01
特許番号
US06987116B2

反応ノート

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