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

HRID 1611528노트

반응식

HRID 1611528 반응식
[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

참가 물질

7

반응물 4

HCID 176Acetic AcidHCID 8083Morpholine2회HCID 5049666Sodium triacetoxyborohydride2회HCID 112248044-[(2,4-Dichloro-5-methoxyphenyl)amino]-2-(4-formylphenyl)thieno[2,3-b]pyridine-5-carbonitrile

생성물 1

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

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

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온도
0 °C

실험 절차

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)+.

후처리

  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

출처 및 근거

ORD 기록
ord-50971320e0514185a485593719cde323
출처 데이터셋
uspto-grants-2006_01
특허 번호
US06987116B2

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