Methylamine → Azd-7624

HRID 337177Notes

Reaction equation

HRID 337177 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1([NH:14][C:15]2[C:16](=[O:35])[N:17]([C:21]3[CH:22]=[C:23]([CH:30]=[C:31]([F:34])[C:32]=3[CH3:33])[C:24]([NH:26][CH:27]3[CH2:29][CH2:28]3)=[O:25])[CH:18]=[CH:19][N:20]=2)[CH2:13][CH2:12]1.[CH3:36][NH2:37]>O1CCOCC1>[CH:27]1([NH:26][C:24](=[O:25])[C:23]2[CH:22]=[C:21]([N:17]3[CH:18]=[CH:19][N:20]=[C:15]([NH:14][C:11]4([C:6]5[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=5[O:4][CH2:3][CH2:2][NH:37][CH3:36])[CH2:13][CH2:12]4)[C:16]3=[O:35])[C:32]([CH3:33])=[C:31]([F:34])[CH:30]=2)[CH2:29][CH2:28]1

Participants

4

Reactant 2

HCID 6329MethylamineHCID 666898043-[3-[[1-[2-(2-chloroethoxy)phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-5-fluoro-4-methyl-benzamide

Product 1

HCID 25143624Azd-7624

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

3-[3-[[1-[2-(2-chloroethoxy)phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-N-cyclopropyl-5-fluoro-4-methyl-benzamide (Example 259d, 10 g) in dioxane (25 mL) was treated with methylamine (15 mL of a 40 wt % aqueous solution). The resulting mixture was stirred at 100° C. for 16 h in a sealed tube. The reaction mixture was cooled, filtered and the solvents removed in vacuo to give crude product (˜10 g). The crude product (˜8.0 g) was purified by RPHPLC (Waters X-Bridge column, 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as mobile phase). The product containing fractions were combined, evaporated and triturated with diethyl ether overnight. The white solid was collected by filtration and dried in vacuo to afford the title compound (4.14 g). NMR consistent with that described above in example 259.

Workup

  1. temperatureThe reaction mixture was cooled
  2. filtrationfiltered
  3. customthe solvents removed in vacuo
  4. customto give crude product (˜10 g)
  5. customThe crude product (˜8.0 g) was purified by RPHPLC (Waters X-Bridge column, 95-5% gradient of aqueous 0.2% ammonia in acetonitrile as mobile phase)
  6. additionThe product containing fractions
  7. customevaporated
  8. customtriturated with diethyl ether overnight
  9. filtrationThe white solid was collected by filtration
  10. customdried in vacuo

Sources & evidence

ORD record
ord-2777278dec4143169975cbe10e59365c
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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