Dichloromethane → 4'-(5-Aminopyrazin-2-yl)-3'-fluoro-N-(2-hydroxyethyl)biphenyl-2-sulfonamide

HRID 1523828ノート

反応式

HRID 1523828 の反応式
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C:17]1[N:18]=[CH:19][C:20]([NH2:23])=[N:21][CH:22]=1.Br[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=1[S:31]([NH:34][CH2:35][CH2:36][OH:37])(=[O:33])=[O:32].C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl>C(OC(=O)C)C.O.O1CCOCC1>[NH2:23][C:20]1[N:21]=[CH:22][C:17]([C:3]2[CH:4]=[CH:5][C:6]([C:25]3[C:26]([S:31]([NH:34][CH2:35][CH2:36][OH:37])(=[O:33])=[O:32])=[CH:27][CH:28]=[CH:29][CH:30]=3)=[CH:7][C:2]=2[F:1])=[N:18][CH:19]=1

参加物

8

反応物 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 435020592-bromo-N-(2-hydroxyethyl)benzenesulfonamideHCID 903122765-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amine

生成物 1

HCID 903126564'-(5-Aminopyrazin-2-yl)-3'-fluoro-N-(2-hydroxyethyl)biphenyl-2-sulfonamide

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
80 °C

実験手順

5-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (40 mg, 0.13 mmol) and 2-bromo-N-(2-hydroxyethyl)benzenesulfonamide (53 mg, 0.19 mmol) were added to a 5 mL sealable vial equipped with a stir bar. 1,4-Dioxane (0.7 mL) and Na2CO3 (0.3 mL, 2 M) were added. Argon was bubbled through the solvent while it was rapidly stirred for 10 min before adding Pd(dppf)Cl2.CH2Cl2 (5 mg, 0.006 mmol) and heating the mixture heated 15 hours at 80° Celsius. The reaction was cooled to rt, diluted with 2 mL of ethylacetate, 2 mL of water and extracted with of ethyl acetate (3×10 mL). The combined organic extracts were then dried with Na2SO4 and concentrated to dryness. The crude product was purified by HPLC to give the title compound. MS (ESI): mass calcd. for C18H17FN4O3S, 388.10; m/z found, 389.1 [M+H]+. 1H NMR (500 MHz, CD3OD) δ 8.43-8.37 (dd, J=2.2, 1.5, 1H), 8.11-8.06 (m, 2H), 7.93-7.86 (m, 1H), 7.70-7.64 (m, 1H), 7.62-7.56 (m, 1H), 7.44-7.38 (dd, J=7.6, 1.3, 1H), 7.35-7.27 (m, 2H), 3.49-3.44 (t, J=5.9, 2H), 2.90-2.84 (t, J=5.9, 2H).

後処理

  1. customequipped with a stir bar
  2. customArgon was bubbled through the solvent while it
  3. additionbefore adding Pd(dppf)Cl2
  4. temperatureThe reaction was cooled to rt
  5. extractionextracted with of ethyl acetate (3×10 mL)
  6. dry with materialThe combined organic extracts were then dried with Na2SO4
  7. concentrationconcentrated to dryness
  8. customThe crude product was purified by HPLC

出典と根拠

ORDレコード
ord-018ff6471be64b05a67a5c07c4caa5dd
出典データセット
uspto-grants-2015_07
特許番号
US09079866B2

反応ノート

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