1-Butanol → 2-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)phenoxy)ethanol

HRID 558153ノート

反応式

HRID 558153 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]2[S:12][C:11]3[C:13]([C:17]4[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=4[O:23][CH2:24][CH2:25][O:26]C4CCCCO4)=[CH:14][CH:15]=[CH:16][C:10]=3[CH:9]=2)[C:5]([F:33])=[CH:4][N:3]=1.[N:34]1([CH2:39][CH2:40][NH2:41])[CH:38]=[CH:37][N:36]=[N:35]1.O1CCOCC1.C(O)CCC>C(O)(C)(C)C.C(Cl)(Cl)Cl.C(O)(C)C.CN1C(=O)CCC1.O1CCOCC1.CN1C(=O)CCC1>[N:34]1([CH2:39][CH2:40][NH:41][C:2]2[N:7]=[C:6]([C:8]3[S:12][C:11]4[C:13]([C:17]5[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=5[O:23][CH2:24][CH2:25][OH:26])=[CH:14][CH:15]=[CH:16][C:10]=4[CH:9]=3)[C:5]([F:33])=[CH:4][N:3]=2)[CH:38]=[CH:37][N:36]=[N:35]1

参加物

9

反応物 4

HCID 2631-ButanolHCID 312751,4-DioxaneHCID 225619722-(1H-1,2,3-Triazol-1-yl)ethanamineHCID 866406622-Chloro-5-fluoro-4-(7-{2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-benzo[b]thiophen-2-yl)-pyrimidine

生成物 1

HCID 592724752-(2-(2-(2-(2-(1H-1,2,3-Triazol-1-yl)ethylamino)-5-fluoropyrimidin-4-yl)benzo[b]thiophen-7-yl)phenoxy)ethanol収率 65%

試薬・触媒・溶媒 4

HCID 6386tert-Butanol溶媒HCID 13387N-methyl-2-pyrrolidone溶媒2 回HCID 17800835dioxane NMP溶媒HCID 21906603Chloroform isopropyl alcohol溶媒

反応条件

温度
135 °C

実験手順

Combine 2-chloro-5-fluoro-4-(7-{2-[2-(tetrahydro-pyran-2-yloxy)-ethoxy]-phenyl}-benzo[b]thiophen-2-yl)-pyrimidine (250 mg, 0.52 mmol) and 2-[1,2,3]triazol-1-yl-ethylamine (140 mg, 1.29 mmol) in tert-butanol (2.6 mL, alternative dioxane, n-butanol, dioxane-NMP, NMP alone as solvent) and NMP (1.3 mL) in a pressure vessel. Heat the mixture in an oil bath at 120-150° C. overnight (or in microwave reactor for a certain period of time). Dilute the mixture with chloroform/IPA (3/1). Wash the solution with aqueous saturated sodium chloride. Dry over sodium sulfate. Concentrate the solution in vacuo. Purify by column chromatography (DCM to 10% methanol in DCM) to give the title compound as a yellow solid (160 mg, 65%). MS (ES) m/z 477 [M+1]+.

後処理

  1. washWash the solution with aqueous saturated sodium chloride
  2. dry with materialDry over sodium sulfate
  3. concentrationConcentrate the solution in vacuo
  4. customPurify by column chromatography (DCM to 10% methanol in DCM)

出典と根拠

ORDレコード
ord-7d6063710fb94076bf585c289e1ea82d
出典データセット
uspto-grants-2011_11
特許番号
US08063035B2

反応ノート

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