Formic Acid → HCID 86610661, compound

HRID 506397Notes

Reaction equation

HRID 506397 reaction equation
[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][C:12](OS(C(F)(F)F)(=O)=O)=[CH:13][CH:14]=2)[C@@H:9]([NH:24][CH:25]([C:40]2[N:45]=[CH:44][C:43]([N:46]3[CH2:51][CH2:50][N:49]([C:52](=[O:54])[CH3:53])[CH2:48][CH2:47]3)=[CH:42][N:41]=2)[C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)[CH2:8][C@H:7]1[CH2:55][CH3:56])=[O:5])[CH3:2].C(N(CC)CC)C.C(O)=O.O>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].C(OCC)(=O)C>[CH2:1]([O:3][C:4]([N:6]1[C:15]2[C:10](=[N:11][CH:12]=[CH:13][CH:14]=2)[C@@H:9]([NH:24][CH:25]([C:40]2[N:45]=[CH:44][C:43]([N:46]3[CH2:47][CH2:48][N:49]([C:52](=[O:54])[CH3:53])[CH2:50][CH2:51]3)=[CH:42][N:41]=2)[C:26]2[CH:27]=[C:28]([C:36]([F:37])([F:39])[F:38])[CH:29]=[C:30]([C:32]([F:33])([F:34])[F:35])[CH:31]=2)[CH2:8][C@H:7]1[CH2:55][CH3:56])=[O:5])[CH3:2]

Participants

9

Reactant 4

HCID 284Formic AcidHCID 962WaterHCID 8471TriethylamineHCID 86610658HCID 86610658, compound

Product 1

HCID 86610661HCID 86610661, compoundYield 95%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

(2R,4S)-4-{[5-(4-Acetylpiperazin-1-yl)pyrimidin-2-yl]-[3,5-bis-(trifluoromethyl)benzyl]}amino-2-ethyl-6-trifluoromethanesulfonyloxy-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (250 mg), palladium acetate (34 mg), 1,1′-bis(diphenylphosphino)ferrocene (84 mg) and triethylamine (126 μl) are dissolved in N,N-dimethylformamide (2 ml), and thereto is added formic acid (28 μl). The mixture is stirred at 60° C. for 1 hour under nitrogen flow. To the reaction solution are added water and ethyl acetate, and then the organic layer is washed with saturated brine and dried over magnesium sulfate, then concentrated under reduced pressure. The resulting residue is purified by column chromatography (NH-silica gel; hexane:ethyl acetate=1:2→0:1) to give (2R,4S)-4-{[5-(4-acetylpiperazin-1-yl)pyrimidin-2-yl]-[3,5-bis(trifluoromethyl)benzyl]}amino-2-ethyl-3,4-dihydro-2H-[1,5]naphthyridine-1-carboxylic acid ethyl ester (195 mg). MS (m/z): 680 [M+H]+.

Workup

  1. washthe organic layer is washed with saturated brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customThe resulting residue is purified by column chromatography (NH-silica gel; hexane:ethyl acetate=1:2→0:1)

Sources & evidence

ORD record
ord-cef67f65bc0948eeafafc503d536a9f4
Source dataset
uspto-grants-2010_08
Patent number
US07781443B2

Reaction notes

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