Ammonium formate → Azd-7624

HRID 869818노트

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HRID 869818 반응식
Br[C:2]1[N:7]=[C:6]([NH:8][C:9]2([C:12]3[CH:32]=[CH:31][CH:30]=[CH:29][C:13]=3[O:14][CH2:15][CH2:16][N:17](C)[C:18](=O)OCC3C=CC=CC=3)[CH2:11][CH2:10]2)[C:5](=[O:33])[N:4]([C:34]2[CH:39]=[C:38]([C:40](=[O:45])[NH:41][CH:42]3[CH2:44][CH2:43]3)[CH:37]=[C:36]([F:46])[C:35]=2[CH3:47])[CH:3]=1.C([O-])=O.[NH4+]>C(O)(C)C.[Pd]>[CH:42]1([NH:41][C:40](=[O:45])[C:38]2[CH:39]=[C:34]([N:4]3[CH:3]=[CH:2][N:7]=[C:6]([NH:8][C:9]4([C:12]5[CH:32]=[CH:31][CH:30]=[CH:29][C:13]=5[O:14][CH2:15][CH2:16][NH:17][CH3:18])[CH2:11][CH2:10]4)[C:5]3=[O:33])[C:35]([CH3:47])=[C:36]([F:46])[CH:37]=2)[CH2:44][CH2:43]1

참가 물질

5

반응물 2

HCID 2723923Ammonium formateHCID 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

생성물 1

HCID 25143624Azd-7624수율 81.9%

시약·촉매·용매 2

HCID 23938Palladium촉매HCID 3776Isopropanol용매

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온도
80 °C

실험 절차

10% Pd/C (87 L paste ex. Johnson Matthey, 110 mg) was washed with isopropanol (10 mL) and then suspended in further isopropanol (10 mL). A sample of this suspension (291 μL, ˜3.2 mg Pd/C) was added to a solution of 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 (Preparation 4e, 10.5 mg, 14.9 μmol) and ammonium formate (33.3 mg, 512 μmol) in isopropanol (0.1 mL). The reaction vessel was sealed and the suspension heated to 80° C. (jacket temperature) for 10 min. The reaction mixture was then filtered through Celite and the cake washed with ethyl acetate. The filtrates were combined and washed with brine that had been basified to pH 12 with KOH. The solution was filtered through a short pad of sodium sulfate and concentrated to dryness in vacuo to afford N-cyclopropyl-3-fluoro-4-methyl-5-[3-[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropylamino]-2-oxo-1(2H)-pyrazinyl]benzamide (6.0 mg) as a colourless solid.

후처리

  1. wash10% Pd/C (87 L paste ex. Johnson Matthey, 110 mg) was washed with isopropanol (10 mL)
  2. customThe reaction vessel was sealed
  3. filtrationThe reaction mixture was then filtered through Celite
  4. washthe cake washed with ethyl acetate
  5. washwashed with brine that
  6. filtrationThe solution was filtered through a short pad of sodium sulfate
  7. concentrationconcentrated to dryness in vacuo

출처 및 근거

ORD 기록
ord-d0f6ee08ed4b4a3f9ee292e5631e059b
출처 데이터셋
uspto-grants-2015_03
특허 번호
US08969350B2

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