Ethanol → HCID 178468258, compound

HRID 84203Notes

Reaction equation

HRID 84203 reaction equation
[OH:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[O:4][N:3]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O:45][C:46](=[O:61])[C@@:47]([OH:60])([CH3:59])[CH2:48][N:49]([CH2:51][C:52]1[CH:57]=[CH:56][C:55](Br)=[CH:54][CH:53]=1)[NH2:50])C.[Cl:62][C:63]1[CH:64]=[CH:65][C:66]([F:72])=[C:67](B(O)O)[CH:68]=1.C([O-])([O-])=O.[K+].[K+].CCO.[Li+].[OH-]>CN(C=O)C.[Pd].O>[Cl:62][C:63]1[CH:68]=[CH:67][C:66]([F:72])=[C:65]([C:55]2[CH:54]=[CH:53][C:52]([CH2:51][N:49]([CH2:48][C@:47]([OH:60])([CH3:59])[C:46]([OH:45])=[O:61])[NH:50][C:7]([C:5]3[O:4][N:3]=[C:2]([OH:1])[CH:6]=3)=[O:9])=[CH:57][CH:56]=2)[CH:64]=1

Participants

12

Reactant 8

HCID 702EthanolHCID 3939Lithium HydroxideHCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 3718925(5-Chloro-2-fluoro-phenyl)boronic acidHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 68180778(R)-3-[N-(4-bromo-benzyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid ethyl esterHCID 178524642HCID 178524642, compound

Product 1

HCID 178468258HCID 178468258, compoundYield 94%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

3-Hydroxyisoxazole-5-carboxylic acid (23.3 mg, 181 μmol) and HATU (68.9 mg, 181 μmol) were combined in DMF (1 mL), and the resulting mixture was stirred for 5 minutes at room temperature. DIPEA (66 μL, 377 μmol) and (R)-3-[N-(4-bromo-benzyl)-hydrazino]-2-hydroxy-2-methyl-propionic acid ethyl ester (50 mg, 0.2 mmol) were added and the resulting mixture was stirred for 20 minutes. The mixture was the evaporated under reduced pressure, then combined with 5-chloro-2-fluorophenylboronic acid (47.4 mg, 272 μmol), K2CO3 (62.6 mg, 453 μmol), EtOH (0.7 mL, 10 mmol), and water (0.2 mL). SilicaCat®DPP-Pd (0.28 mmol/g loading; 53.9 mg, 15 μmol) was added and the resulting mixture was microwaved at 120° C. for 10 minutes. The mixture was filtered, and 1 M aqueous LiOH (604 μL, 604 μmol) was added. The mixture was stirred for 1 hour, then concentrated and purified by preparative HPLC to yield the title compound (33 mg, 94% purity). MS m/z [M+H]+ calc'd for C21H19ClFN3O6, 464.09; Found 464.1.

Workup

  1. stirringthe resulting mixture was stirred for 20 minutes
  2. customevaporated under reduced pressure
  3. customthe resulting mixture was microwaved at 120° C. for 10 minutes
  4. filtrationThe mixture was filtered
  5. stirringThe mixture was stirred for 1 hour
  6. concentrationconcentrated
  7. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-008f989b3d464a8c8e8599c09f354d41
Source dataset
uspto-grants-2014_09
Patent number
US08846913B2

Reaction notes

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