Diisopropylethylamine → N1-(2-(2-hydroxyethoxy)ethyl)-N3-(4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)isophthalamide

HRID 2406085Notes

Reaction equation

HRID 2406085 reaction equation
[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][C:8]([C:10]1[CH:11]=[C:12]([CH:16]=[CH:17][CH:18]=1)[C:13]([OH:15])=O)=[O:9].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)C(C)C)C.[NH2:52][C:53]1[CH:77]=[CH:76][C:75]([N:78]2[CH2:83][CH2:82][CH2:81][CH2:80][CH2:79]2)=[CH:74][C:54]=1[C:55]([NH:57][C:58]1[CH:63]=[N:62][C:61]([C:64]2[CH:69]=[CH:68][CH:67]=[C:66]([C:70]([F:73])([F:72])[F:71])[CH:65]=2)=[CH:60][N:59]=1)=[O:56]>CN(C)C=O.C(OCC)(=O)C>[OH:1][CH2:2][CH2:3][O:4][CH2:5][CH2:6][NH:7][C:8](=[O:9])[C:10]1[CH:18]=[CH:17][CH:16]=[C:12]([C:13]([NH:52][C:53]2[CH:77]=[CH:76][C:75]([N:78]3[CH2:83][CH2:82][CH2:81][CH2:80][CH2:79]3)=[CH:74][C:54]=2[C:55](=[O:56])[NH:57][C:58]2[CH:63]=[N:62][C:61]([C:64]3[CH:69]=[CH:68][CH:67]=[C:66]([C:70]([F:73])([F:72])[F:71])[CH:65]=3)=[CH:60][N:59]=2)=[O:15])[CH:11]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665867923-((2-(2-Hydroxyethoxy)ethyl)carbamoyl)benzoic acidHCID 665868902-amino-5-(piperidin-1-yl)-N-(5-(3-(trifluoromethyl)phenyl)-pyrazin-2-yl)benzamide

Product 1

HCID 56601993N1-(2-(2-hydroxyethoxy)ethyl)-N3-(4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)isophthalamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Into a 50-mL round bottom flask, was placed a solution of 3-((2-(2-hydroxyethoxy)-ethyl)carbamoyl)benzoic acid (189.3 mg, 0.75 mmol, 1.10 equiv) in N,N-dimethylformamide (2.5 mL), HATU (1034 mg, 2.72 mmol, 4.00 equiv), and N-ethyl-N-isopropylpropan-2-amine (351 mg, 2.72 mmol, 4.00 equiv). This was followed by dropwise addition of a solution of 2-amino-5-(piperidin-1-yl)-N-(5-(3-(trifluoromethyl)phenyl)-pyrazin-2-yl)benzamide (300 mg, 0.68 mmol, 1.00 equiv) in N,N-dimethylformamide (2.5 mL) with stirring. The resulting solution was stirred overnight at 40° C. in an oil bath. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 2×20 mL of brine, dried over anhydrous sodium sulfate, and concentrated under vacuum. The crude product was purified by reverse phase HPLC eluting with 0.05% TFA in a water/CH3CN gradient.

Workup

  1. customInto a 50-mL round bottom flask, was placed
  2. stirringThe resulting solution was stirred overnight at 40° C. in an oil bath
  3. washThe resulting mixture was washed with 2×20 mL of brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product was purified by reverse phase HPLC
  7. washeluting with 0.05% TFA in a water/CH3CN gradient

Sources & evidence

ORD record
ord-1ae8c89d6691479f8818be499c9e94d9
Source dataset
uspto-grants-2014_08
Patent number
US08809339B2

Reaction notes

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