Ethyl Acetate → Benzyl[2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate

HRID 869816ノート

反応式

HRID 869816 の反応式
[CH:1]1([NH2:4])[CH2:3][CH2:2]1.[CH:5]([Mg]Cl)([CH3:7])[CH3:6].[CH:10]1([NH-])[CH2:12][CH2:11]1.Cl[Mg+].C(OC([CH2:26][NH:27][CH2:28][CH2:29][O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:37]1([NH:40][C:41]2[C:42](=[O:60])[N:43]([C:48]3[CH:49]=[C:50]([CH:55]=[C:56]([F:59])[C:57]=3[CH3:58])[C:51]([O:53]C)=O)[CH:44]=[C:45]([Br:47])[N:46]=2)[CH2:39][CH2:38]1)=O)C1C=CC=CC=1.[C:61]([O:64][CH2:65]C)(=[O:63])C>C1COCC1>[Br:47][C:45]1[N:46]=[C:41]([NH:40][C:37]2([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=3[O:30][CH2:29][CH2:28][N:27]([CH3:26])[C:61](=[O:63])[O:64][CH2:65][C:12]3[CH:10]=[CH:7][CH:5]=[CH:6][CH:11]=3)[CH2:38][CH2:39]2)[C:42](=[O:60])[N:43]([C:48]2[CH:49]=[C:50]([C:51](=[O:53])[NH:4][CH:1]3[CH2:3][CH2:2]3)[CH:55]=[C:56]([F:59])[C:57]=2[CH3:58])[CH:44]=1

参加物

7

反応物 5

HCID 8857Ethyl AcetateHCID 69828CyclopropylamineHCID 66713357methyl 3-[3-[1-[2-[2-[(benzyloxycarbonyl)methylamino]ethoxy]phenyl]cyclopropylamino]-5-bromo-2-oxo-1(2H)-pyrazinyl]-5-fluoro-4-methylbenzoateHCID 178418918HCID 178418918、化合物HCID 178507068HCID 178507068、化合物

生成物 1

HCID 58072137Benzyl[2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

A solution of cyclopropylamine (261.9 μL, 3.70 mmol) in dry THF (2 mL) under an inert atmosphere was chilled in an ice-water bath and freshly titrated isopropylmagnesium chloride (1.46 M in THF, 1.27 mL, 1.85 mmol) was added. A portion of this chloromagnesium cyclopropylamide solution (0.524 M in THF, 2.12 mL, 1.11 mmol) was added via syringe to a stirred solution of methyl 3-[3-[1-[2-[2-[(benzyloxycarbonyl)methylamino]ethoxy]phenyl]cyclopropylamino]-5-bromo-2-oxo-1(2H)-pyrazinyl]-5-fluoro-4-methylbenzoate (Preparation 4d, 125.7 mg, 185 μmol) in dry THF (2 mL) under an inert atmosphere. After 30 min, ethyl acetate (1 mL) was added before the reaction mixture was poured into ice-cold saturated aq. ammonium chloride (10 mL) and extracted with diethyl ether (3×10 mL). The organic extracts were combined, washed with brine (30 mL), dried over sodium sulfate and concentrated in vacuo. The residue was purified by preparative TLC on silica, eluting with ethyl acetate/isohexane/methanol (50:50:1 v/v), to afford benzyl [2-[2-[1-[[6-bromo-4-[5-(cyclopropylcarbamoyl)-3-fluoro-2-methylphenyl]-3-oxo-3,4-dihydro-2-pyrazinyl]amino]cyclopropyl]phenoxy]ethyl]methylcarbamate (79.4 mg) as a white foam.

後処理

  1. extractionextracted with diethyl ether (3×10 mL)
  2. washwashed with brine (30 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by preparative TLC on silica
  6. washeluting with ethyl acetate/isohexane/methanol (50:50:1 v/v)

出典と根拠

ORDレコード
ord-c435206250694047a578778ec3eb0161
出典データセット
uspto-grants-2015_03
特許番号
US08969350B2

反応ノート

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