3-Chloro-4-fluoroaniline → (3-Chloro-4-fluoro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine

HRID 38514

反応式

HRID 38514 の反応式
Cl[C:2]1[C:3]2[C:10]3[CH2:11][CH2:12][N:13](C(OC(C)(C)C)=O)[CH2:14][C:9]=3[S:8][C:4]=2[N:5]=[CH:6][N:7]=1.[Cl:22][C:23]1[CH:24]=[C:25]([CH:27]=[CH:28][C:29]=1[F:30])[NH2:26].O1CCOCC1>CC(O)C.Cl.O1CCOCC1>[Cl:22][C:23]1[CH:24]=[C:25]([NH:26][C:2]2[C:3]3[C:10]4[CH2:11][CH2:12][NH:13][CH2:14][C:9]=4[S:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:27]=[CH:28][C:29]=1[F:30]

参加物

7

反応物 3

HCID 97083-Chloro-4-fluoroanilineHCID 312751,4-DioxaneHCID 49788563tert-Butyl 4-chloro-5,6-dihydropyrido(4',3':4,5)thieno(2,3-d)pyrimidine-7(8H)-carboxylate

生成物 1

HCID 58116889(3-Chloro-4-fluoro-phenyl)-(5,6,7,8-tetrahydro-9-thia-1,3,7-triaza-fluoren-4-yl)-amine収率 95%

試薬・触媒・溶媒 3

HCID 312751,4-Dioxane触媒HCID 313Hydrochloric Acid溶媒2 回HCID 3776Isopropanol溶媒2 回

反応条件

温度
80 °C

実験手順

tert-Butyl 4-chloro-5,8-dihydropyrido[4′,3′:4,5]thieno[2,3-d]pyrimidine-7(6H)-carboxylate from Example 11A (407.5 g, 1.251 mol) was dissolved in 2-propanol (5.7 L). 3-Chloro-4-fluoroaniline (191.2 g, 1.313 mol) and a 4 M solution of gaseous hydrogen chloride in dioxane (17.4 mL, 63 mmol) were added. The mixture was heated to 80° C. for 3 days. The thick suspension was then diluted with additional 2-propanol (1 L), and further 4 M hydrogen chloride in dioxane (695 mL, 2.5 mol) was added. The mixture was again heated to 80° C. for 3 h. The solvent was then removed in vacuo, and the residue was treated with 1 M aqueous sodium hydroxide solution (12 L). The precipitate was collected by suction filtration and washed with water. The product was dried for 2 days at 50° C., then triturated with tert-butyl methyl ether and collected by suction filtration to yield 397 g (95%) of the title compound.

後処理

  1. additionwas added
  2. temperatureThe mixture was again heated to 80° C. for 3 h
  3. customThe solvent was then removed in vacuo
  4. additionthe residue was treated with 1 M aqueous sodium hydroxide solution (12 L)
  5. filtrationThe precipitate was collected by suction filtration
  6. washwashed with water
  7. customThe product was dried for 2 days at 50° C.
  8. customtriturated with tert-butyl methyl ether
  9. filtrationcollected by suction filtration

出典と根拠

ORDレコード
ord-ad282380db8c4a4baa457cc3f1261e56
出典データセット
uspto-grants-2013_09
特許番号
US08524722B2

関連ノート

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