Ammonium formate → Azd-7624

HRID 869818Notes

Reaction equation

HRID 869818 reaction equation
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

Participants

5

Reactant 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

Product 1

HCID 25143624Azd-7624Yield 81.9%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 3776IsopropanolSolvent

Conditions

Temperature
80 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-d0f6ee08ed4b4a3f9ee292e5631e059b
Source dataset
uspto-grants-2015_03
Patent number
US08969350B2

Reaction notes

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