Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → 3-{5-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorophenyl}-5-methylimidazolidine-2,4-dione

HRID 1172804Notes

Reaction equation

HRID 1172804 reaction equation
C(O[C:4]([NH:6][C@H:7]([C:9]([OH:11])=O)[CH3:8])=[O:5])C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.FC(F)(F)C([O-])=O.[Cl:43][C:44]1[N:48]2[C:49]([CH2:54][C:55]3[CH:56]=[CH:57][C:58]([F:62])=[C:59]([NH3+:61])[CH:60]=3)=[CH:50][NH:51][C:52](=[O:53])[C:47]2=[CH:46][C:45]=1[Cl:63]>CN(C=O)C.CN(C1C=CN=CC=1)C.C(Cl)Cl.O.CC#N>[Cl:43][C:44]1[N:48]2[C:49]([CH2:54][C:55]3[CH:56]=[CH:57][C:58]([F:62])=[C:59]([N:61]4[C:9](=[O:11])[CH:7]([CH3:8])[NH:6][C:4]4=[O:5])[CH:60]=3)=[CH:50][NH:51][C:52](=[O:53])[C:47]2=[CH:46][C:45]=1[Cl:63]

Participants

9

Reactant 3

HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 10558934N-(Ethoxycarbonyl)alanineHCID 866334295-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorobenzenaminium trifluoroacetate

Product 1

HCID 686870153-{5-[(6,7-Dichloro-1-oxo-1,2-dihydropyrrolo[1,2-a]pyrazin-4-yl)methyl]-2-fluorophenyl}-5-methylimidazolidine-2,4-dione

Reagents, catalysts & solvents 5

HCID 142844-(Dimethylamino)pyridineCatalyst2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

N-(Ethoxycarbonyl)alanine* (1.35 eq) and HATU (1.35 eq) in DMF (0.1 M) were stirred at RT for 20 min and then N2 (Example 14, step 2) (1 eq) and DMAP (1.35 eq) were added. The reaction mixture was stirred at RT overnight. The reaction mixture was diluted with DCM and washed with 1N HCl solution and brine. The organic phase was dried (Na2SO4), filtered and concentrated. The resulting crude was dissolved in DMF (0.1 M) and DMAP (1 eq) was added. The mixture was heated in a microwave oven at 180° C. for 50 min. The product was isolated by purification at prep RP-HPLC using H2O (+0.1% TFA) and MeCN (+0.1% TFA) as eluents. The desired fractions were lyophilized to afford the desired compound. 1H NMR (400 MHz, DMSO-d6) δ: 10.91 (1H, d, J=5.6 Hz), 8.51 (1H, s), 7.37-7.23 (3H, m), 7.15 (1H, s), 6.54 (1H, d, J=5.6 Hz), 4.38 (2H, s), 4.35-4.24 (1H, m), 1.41-1.30 (3H, m). MS (ES) C18H13Cl2FN4O3 requires: 422/424, found: 423/425 (M+H)+.

Workup

  1. washwashed with 1N HCl solution and brine
  2. dry with materialThe organic phase was dried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe resulting crude was dissolved in DMF (0.1 M)
  6. temperatureThe mixture was heated in a microwave oven at 180° C. for 50 min
  7. customThe product was isolated by purification at prep RP-HPLC

Sources & evidence

ORD record
ord-2037dff4d182495e8e5c91a5abd671c1
Source dataset
uspto-grants-2010_11
Patent number
US07834015B2

Reaction notes

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