Pyridine → N-{3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-acetamide

HRID 1861076ノート

反応式

HRID 1861076 の反応式
[CH3:1][N:2]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:27]=[CH:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[N:15][N:16]2COCC[Si](C)(C)C)=[CH:12][CH:11]=1)[C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([NH2:9])[CH:4]=1.N1C=CC=CC=1.[CH3:41][C:42](OC(C)=O)=[O:43].C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl.CN(C1C=CN=CC=1)C.CCOC(C)=O.C(Cl)Cl.CCOC(C)=O>[CH3:1][N:2]([C:10]1[CH:18]=[C:17]2[C:13]([C:14]([CH:27]=[CH:28][C:29]3[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=3)=[N:15][NH:16]2)=[CH:12][CH:11]=1)[C:3]1[CH:4]=[C:5]([NH:9][C:42](=[O:43])[CH3:41])[CH:6]=[CH:7][CH:8]=1

参加物

9

反応物 4

HCID 1049PyridineHCID 7918Acetic AnhydrideHCID 11430Potassium CarbonateHCID 69369951HCID 69369951、化合物

生成物 1

HCID 69370837N-{3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-acetamide収率 22%

試薬・触媒・溶媒 4

HCID 142844-(Dimethylamino)pyridine触媒HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 21226138Dichloromethane ethylacetate溶媒

反応条件

温度
23 °C

実験手順

N-Methyl-N-{3-styryl-1-[2-(trimethyl-silanyl)-ethoxymethyl]-1H-indazol-6-yl}-benzene-1,3-diamine, prepared in Example 11 (34 mg, 0.041 mmol) was suspended in CH2Cl2 (0.5 mL) at 23° C. under an atmosphere of argon. Pyridine (81 pi, 1.0 mmol), Ac2O (94 μl, 1.0 mmol) and DMAP (cat.) were added. The reaction became homogeneous immediately. After 1 h, TLC analysis (CH2Cl2:EtOAc 4:1) indicated no starting material. The reaction was quenched with saturated NaHCO3 (aq) (2 mL) then diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure to an oil. The oil was suspended in MeOH (2 mL) and K2CO3 (83 mg, 0.6 mmol) was added. The resulting mixture was stirred at 23° C. under an atmosphere of argon. After 1 h, the reaction was diluted with EtOAc (15 mL) and the organic phase was washed with brine (3 mL), decanted and concentrated under reduced pressure. The crude material was purified by semi-prep HPLC to give N-{3-[methyl-(3-styryl-1H-indazol-6-yl)-amino]-phenyl}-acetamide (8.4 mg, 22%). 1H NMR (300 MHz, CDCl3) δ 7.86 (d, 1H, J=8.68 Hz), 7.58 (d, 1H, J=7.17 Hz), 7.16-7.45 (m, 7H), 7.15 (d, 1H, J=8.29 Hz), 6.98 (m, 1H), 6.95 (d, 1H, J=1.92 Hz), 6.8 (dd, 1H, J=1.16,8.05 Hz), 3.37 (s, 3H), 2.14 (s, 3H). LCMS (ESI) [M+H]/z Calc'd 383, Found 383. Anal. Calc'd: C, 75.37; H, 5.80; N, 14.65. Found: C, 73.53; H, 6.01; N, 13.73.

後処理

  1. customThe reaction was quenched with saturated NaHCO3 (aq) (2 mL)
  2. additionthen diluted with EtOAc (15 mL)
  3. washthe organic phase was washed with brine (3 mL)
  4. customdecanted
  5. concentrationconcentrated under reduced pressure to an oil
  6. waitAfter 1 h
  7. washthe organic phase was washed with brine (3 mL)
  8. customdecanted
  9. concentrationconcentrated under reduced pressure
  10. customThe crude material was purified by semi-prep HPLC

出典と根拠

ORDレコード
ord-7b864713f84a4bf19a4ea8ce9c69e940
出典データセット
uspto-grants-2003_03
特許番号
US06531491B1

反応ノート

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