Trifluoroacetic acid → Trifluoroacetate

HRID 1522047ノート

反応式

HRID 1522047 の反応式
CC1(C)C(C)(C)OB([C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[NH:15][C:16]([CH:18]4[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]4)=[CH:17][C:10]=23)O1.[CH2:32]([NH:39][C:40]1[CH:45]=[N:44][CH:43]=[C:42](Br)[N:41]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])[O-].[Cs+].[Cs+].[F:72][C:73]([F:78])([F:77])[C:74]([OH:76])=[O:75]>C(Cl)Cl.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCOCC1>[CH2:32]([NH:39][C:40]1[CH:45]=[N:44][CH:43]=[C:42]([C:9]2[CH:14]=[CH:13][N:12]=[C:11]3[NH:15][C:16]([CH:18]4[CH2:19][CH2:20][NH:21][CH2:22][CH2:23]4)=[CH:17][C:10]=23)[N:41]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.[F:72][C:73]([F:78])([F:77])[C:74]([O-:76])=[O:75]

参加物

10

反応物 5

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 90412512HCID 90412512、化合物HCID 90413258HCID 90413258、化合物

生成物 2

HCID 84468TrifluoroacetateHCID 90412090HCID 90412090、化合物

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 6344Dichloromethane溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

A mixture of Example 21A (400 mg, 0.94 mmol), N-benzyl-6-bromopyrazin-2-amine (297 mg, 1.12 mmol), bis(triphenylphosphine)palladium(ii) chloride (66 mg, 0.094 mmol), tricyclohexylphosphine (26 mg, 0.094 mmol) and cesium carbonate (921 mg, 2.8 mmol) was purged with nitrogen, then anhydrous dioxane (50 mL) was added. The mixture was heated at 100° C. overnight. The reaction was cooled to room temperature and filtrated; and the solid was washed with dichloromethane (200 mL). The filtrate was concentrated and purified by flash chromatography on silica gel using an ISCO Companion eluting with heptanes/ethyl acetate (30%) to give Boc-protected intermediate that was dissolved in CH2Cl2 (10 mL) then treated with trifluoroacetic acid (1 mL). The mixture was stirred at room temperature for 5 hours and concentrated. The residue was purified by reverse-phase HPLC on Zorbax XDB C-18 using a gradient of 5-40% acetonitrile/water (containing 0.1% trifluoroacetic acid) to afford the title compound as trifluoroacetate salt. MS (DCI/NH3) m/z 385 (M+H)+.

後処理

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltrated
  3. washand the solid was washed with dichloromethane (200 mL)
  4. concentrationThe filtrate was concentrated
  5. custompurified by flash chromatography on silica gel using an ISCO Companion
  6. washeluting with heptanes/ethyl acetate (30%)
  7. customto give Boc-protected intermediate
  8. concentrationconcentrated
  9. customThe residue was purified by reverse-phase HPLC on Zorbax XDB C-18

出典と根拠

ORDレコード
ord-13c3b27ef2f14c85a0ded93e92e5180a
出典データセット
uspto-grants-2015_07
特許番号
US09073922B2

反応ノート

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