Tetrahydrofuran → Tert-butyl 5-(3-(4-amino-6-methyl-1,3,5-triazin-2-YL)-5-methoxypyridin-2-ylamino)-2-chloropyridin-3-ylcarbamate

HRID 1622012

反応式

HRID 1622012 の反応式
[NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])[C:5]([Cl:8])=[N:6][CH:7]=1.F[C:18]1[C:23]([C:24]2[N:29]=[C:28]([CH3:30])[N:27]=[C:26]([NH2:31])[N:25]=2)=[CH:22][C:21]([O:32][CH3:33])=[CH:20][N:19]=1.C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C1COCC1.[NH4+].[Cl-]>CN(C=O)C>[NH2:31][C:26]1[N:27]=[C:28]([CH3:30])[N:29]=[C:24]([C:23]2[C:18]([NH:1][C:2]3[CH:3]=[C:4]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:13])([CH3:15])[CH3:14])[C:5]([Cl:8])=[N:6][CH:7]=3)=[N:19][CH:20]=[C:21]([O:32][CH3:33])[CH:22]=2)[N:25]=1

参加物

7

反応物 5

HCID 8028TetrahydrofuranHCID 25517Ammonium ChlorideHCID 2724254Sodium bis(trimethylsilyl)amideHCID 666111694-(2-Fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amineHCID 86647086Tert-butyl 5-amino-2-chloropyridin-3-ylcarbamate

生成物 1

HCID 86647088Tert-butyl 5-(3-(4-amino-6-methyl-1,3,5-triazin-2-YL)-5-methoxypyridin-2-ylamino)-2-chloropyridin-3-ylcarbamate収率 85.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
0 °C

実験手順

To a 15 mL RB flask was added tert-butyl 5-amino-2-chloropyridin-3-ylcarbamate (0.130 g, 0.533 mmol), 4-(2-fluoro-5-methoxypyridin-3-yl)-6-methyl-1,3,5-triazin-2-amine (Example 330 step 5)(0.151 g, 0.640 mmol), and DMF (2.0 mL). The mixture was cooled to 0° C. under N2. Sodium bis(trimethylsilyl)amide, 1.0 m in THF (Aldrich) (2.134 mL, 2.134 mmol) was then added to the solution in one portion. The now burgundy color mixture was stirred at 0° C. for 10 min then warmed up to rt and stirred for 30 min. The reaction mixture was poured into the beaker which had filled with 15 mL sat. NH4Cl. The resulting mixture was stirred at rt for 5 h. The ppt in the solution mixture was collected by filtration. The solid was rinsed with water and dried opened to the air for 4 h. This crude product was purified by column chromatography (40 g, 3% MeOH in DCM) to afford the desired product as a yellow solid (210 mg). MS (ESI pos. ion) m/z: 459.0. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.47 (s, 9H) 2.45 (s, 3H) 3.85 (s, 3H) 7.80 (br. s., 1H) 7.94 (br. s., 1H) 8.20 (d, J=3.07 Hz, 1H) 8.42 (d, J=3.07 Hz, 1H) 8.58 (d, J=2.34 Hz, 1H) 8.63 (d, J=2.34 Hz, 1H) 8.75 (s, 1H) 11.91 (s, 1H).

後処理

  1. temperaturethen warmed up to rt
  2. stirringstirred for 30 min
  3. additionThe reaction mixture was poured into the beaker which
  4. stirringThe resulting mixture was stirred at rt for 5 h
  5. filtrationThe ppt in the solution mixture was collected by filtration
  6. washThe solid was rinsed with water
  7. customdried
  8. waitopened to the air for 4 h
  9. customThis crude product was purified by column chromatography (40 g, 3% MeOH in DCM)

出典と根拠

ORDレコード
ord-48225d64c5ba42dfbaccb0b15b7e869e
出典データセット
uspto-grants-2014_07
特許番号
US08772480B2

関連ノート

読み込み中…