2-(Trimethylsilyl)ethanol → tert-Butyl 4-(5-(8-morpholino-2-(((2-(trimethylsilyl)ethoxy)carbonyl)amino)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

HRID 718601ノート

反応式

HRID 718601 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]([C:14]2[N:19]=[CH:18][C:17]([C:20]3[N:24]4[N:25]=[CH:26][CH:27]=[C:28]([N:29]5[CH2:34][CH2:33][O:32][CH2:31][CH2:30]5)[C:23]4=[N:22][C:21]=3C(O)=O)=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:38](Cl)(=[O:42])C(Cl)=O.[Si]([N:48]=[N+]=[N-])(C)(C)C.[CH3:51][Si:52]([CH3:57])([CH3:56])[CH2:53][CH2:54][OH:55]>CN(C=O)C.C(Cl)Cl>[O:32]1[CH2:33][CH2:34][N:29]([C:28]2[C:23]3[N:24]([C:20]([C:17]4[CH:16]=[CH:15][C:14]([N:11]5[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:7])[CH2:13][CH2:12]5)=[N:19][CH:18]=4)=[C:21]([NH:48][C:38]([O:55][CH2:54][CH2:53][Si:52]([CH3:57])([CH3:56])[CH3:51])=[O:42])[N:22]=3)[N:25]=[CH:26][CH:27]=2)[CH2:30][CH2:31]1

参加物

7

反応物 4

HCID 180132-(Trimethylsilyl)ethanolHCID 65578Oxalyl chlorideHCID 78378Azidotrimethylsilane2 回HCID 1177284223-(6-(4-(tert-Butoxycarbonyl)piperazin-1-yl)pyridin-3-yl)-8-morpholinoimidazo[1,2-b]pyridazine-2-carboxylic acid

生成物 1

HCID 123846403tert-Butyl 4-(5-(8-morpholino-2-(((2-(trimethylsilyl)ethoxy)carbonyl)amino)imidazo[1,2-b]pyridazin-3-yl)pyridin-2-yl)piperazine-1-carboxylate

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 6344Dichloromethane溶媒

反応条件

温度
100 °C

実験手順

Compound 20c (250 mg, 0.491 mmol) was placed in a 20 mL vial equipped with a stir bar and then DCM (4 mL) and DMF (10 μL) were added. Oxalyl chloride (100 μL, 1.15 mmol) was added dropwise via syringe and then the reaction was stirred for 20 min. The solvent was removed under reduced pressure. The residue was dissolved in DCM (25 mL) and then TMSN3 (100 μL, 0.760 mmol) was added. The reaction was stirred at rt for 16 h and then additional TMSN3 (100 μL, 0.760 mmol) was added. The reaction was stirred at rt for 24 h and then the solvent was removed under reduced pressure. The residue was dissolved in toluene (10 mL) and then 2-(trimethylsilyl)ethanol (1 mL, 7 mmol) was added. The flask was fitted with a reflux condenser and heated to 100° C. for 3 h. The reaction was cooled to rt and then the solvent was removed under reduced pressure. The residue was chromatographed on a 12 g SiO2 pre-packed column eluting with 0-80% ACN/DCM to afford compound 23a. 1H-NMR (400 MHz, CDCl3) δ (ppm): 8.51 (d, J=2.2 Hz, 1H), 7.99 (d, J=5.6 Hz, 1H), 7.90 (dd, J=8.9, 2.3 Hz, 1H), 6.73 (d, J=8.8 Hz, 1H), 6.70 (s, 1H), 6.09 (d, J=5.6 Hz, 1H), 4.10-4.20 (m, 2H), 3.84-3.96 (m, 8H), 3.50-3.62 (m, 8H), 1.49 (s, 9H), 0.00 (s, 9H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C30H44N8O5Si: 625.3 (M+H). Found: 625.3.

後処理

  1. customvial equipped with a stir bar
  2. customThe solvent was removed under reduced pressure
  3. dissolutionThe residue was dissolved in DCM (25 mL)
  4. stirringThe reaction was stirred at rt for 16 h
  5. stirringThe reaction was stirred at rt for 24 h
  6. customthe solvent was removed under reduced pressure
  7. dissolutionThe residue was dissolved in toluene (10 mL)
  8. customThe flask was fitted with a reflux condenser
  9. temperatureThe reaction was cooled to rt
  10. customthe solvent was removed under reduced pressure
  11. customThe residue was chromatographed on a 12 g SiO2 pre-packed column
  12. washeluting with 0-80% ACN/DCM

出典と根拠

ORDレコード
ord-7c2a87934b264f949a22707e5d3dbdfe
出典データセット
uspto-grants-2015_11
特許番号
US09193736B2

反応ノート

読み込み中…