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 869816노트

반응식

HRID 869816 반응식
[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

참가 물질

7

반응물 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, 화합물HCID 178507068HCID 178507068, 화합물

생성물 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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-c435206250694047a578778ec3eb0161
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969350B2

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