5-Prop-2-ynyloxypyrazine-2-carboxylic acid → N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-(prop-2-yn-1-yloxy)pyrazine-2-carboxamide

HRID 930296Notes

Reaction equation

HRID 930296 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([F:20])=[C:6]([C@:8]2([CH3:19])[CH2:13][C@@H:12]([C:14]([F:17])([F:16])[F:15])[O:11][C:10]([NH2:18])=[N:9]2)[CH:7]=1.[CH2:21]([O:24][C:25]1[N:26]=[CH:27][C:28]([C:31](O)=[O:32])=[N:29][CH:30]=1)[C:22]#[CH:23]>>[NH2:18][C:10]1[O:11][C@H:12]([C:14]([F:16])([F:17])[F:15])[CH2:13][C@:8]([C:6]2[CH:7]=[C:2]([NH:1][C:31]([C:28]3[CH:27]=[N:26][C:25]([O:24][CH2:21][C:22]#[CH:23])=[CH:30][N:29]=3)=[O:32])[CH:3]=[CH:4][C:5]=2[F:20])([CH3:19])[N:9]=1

Participants

3

Reactant 2

HCID 584486085-Prop-2-ynyloxypyrazine-2-carboxylic acidHCID 71663148(4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine2×

Product 1

HCID 86732127N-(3-((4S,6S)-2-amino-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-4-yl)-4-fluorophenyl)-5-(prop-2-yn-1-yloxy)pyrazine-2-carboxamide

Procedure

The title compound was synthesized by procedures and steps analogous to those described in Method F (Example 32) above, but using (4S,6S)-4-(5-amino-2-fluorophenyl)-4-methyl-6-(trifluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate 4i) and 5-(prop-2-yn-1-yloxy)pyrazine-2-carboxylic acid (J. Med. Chem. 2013, 56, 3980). The desired product was purified by reversed-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 100×50 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 80% over 20 min. The product containing fractions were combined and neutralized with 1N NaOH solution. The free-based product was extracted with DCM. The organic phase was dried over Na2SO4 and the solvent was removed under reduced pressure to afford the title compound. MS m/z=452.1 [M+H]+. Calculated for C20H17ClF4N5O3: 451.1

Workup

  1. customThe title compound was synthesized by procedures and steps analogous to
  2. customThe desired product was purified by reversed-phase preparative HPLC
  3. customover 20 min
  4. additionThe product containing fractions
  5. extractionThe free-based product was extracted with DCM
  6. dry with materialThe organic phase was dried over Na2SO4
  7. customthe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-076c9ea745ef45c58476a0cb306cff3e
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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