Dimethylamine → 7-[(2,4-Dichloro-5-methoxyphenyl)amino]-3-{4-[(dimethylamino)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrile

HRID 1178684노트

반응식

HRID 1178684 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[C:20]([C:23]3[CH:28]=[CH:27][C:26]([CH:29]=O)=[CH:25][CH:24]=3)=[CH:21][S:22][C:13]=12.[CH3:31][NH:32][CH3:33].O1CCCC1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl.C(O)(=O)C.CN(C)C=O>[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[C:20]([C:23]3[CH:24]=[CH:25][C:26]([CH2:29][N:32]([CH3:33])[CH3:31])=[CH:27][CH:28]=3)=[CH:21][S:22][C:13]=12

참가 물질

8

반응물 4

HCID 674DimethylamineHCID 8028TetrahydrofuranHCID 5049666Sodium triacetoxyborohydrideHCID 117513977-[(2,4-Dichloro-5-methoxyphenyl)amino]-3-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile

생성물 1

HCID 116774257-[(2,4-Dichloro-5-methoxyphenyl)amino]-3-{4-[(dimethylamino)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrile수율 69%

시약·촉매·용매 3

HCID 176Acetic Acid촉매HCID 6228Dimethylformamide용매HCID 6344Dichloromethane용매

실험 절차

A mixture of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-3-(4-formylphenyl)thieno[3,2-b]pyridine-6-carbonitrile (200 mg, 0.44 mmol) and 1.1 mL of a 2 M solution of dimethylamine in tetrahydrofuran (2.20 mmol) in 5 mL of dichloromethane and 1 mL of dimethylformamide is cooled to 0° C. Sodium triacetoxyborohydride (560 mg, 2.64 mmol) is added in portions followed by 3 drops of acetic acid. The resulting mixture is stirred at room temperature for 2.5 hours then quenched by the addition of water. The mixture is partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The organic phase is washed with saturated aqueous sodium chloride, dried over sodium sulfate, filtered and concentrated in vacuo. The residue is purified by flash column chromatography eluting with a gradient of methanol in dichloromethane to provide 147 mg (69%) of 7-[(2,4-dichloro-5-methoxyphenyl)amino]-3-{4-[(dimethylamino)methyl]phenyl}thieno[3,2-b]pyridine-6-carbonitrile as a white solid, mp 201–202° C.; 1 H NMR (DMSO-d6) δ 2.19 (s, 6H), 3.46 (s, 2H), 3.86 (s, 3H), 7.38 (d, J=8 Hz, 2H), 7.42 (s, 1H), 7.78 (s, 1H), 7.89 (d, J=8 Hz, 2H), 8.31 (s, 1H), 8.69 (s, 1H), 9.78 (s, 1H); MS 483.0, 485.0 (M+H)+; HRMS found: 483.08061 (M+H)+.

후처리

  1. customthen quenched by the addition of water
  2. customThe mixture is partitioned between dichloromethane and saturated aqueous sodium bicarbonate
  3. washThe organic phase is washed with saturated aqueous sodium chloride
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue is purified by flash column chromatography
  8. washeluting with a gradient of methanol in dichloromethane

출처 및 근거

ORD 기록
ord-06cc8d941f9a4644bc3685832162bf86
출처 데이터셋
uspto-grants-2007_10
특허 번호
US07276519B2

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