Diisopropylethylamine → Tert-butyl 3-(3-((4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)carbamoyl)benzylthio)propanoate

HRID 2406099Notes

Reaction equation

HRID 2406099 reaction equation
[C:1]([O:5][C:6](=[O:20])[CH2:7][CH2:8][S:9][CH2:10][C:11]1[CH:12]=[C:13]([CH:17]=[CH:18][CH:19]=1)[C:14]([OH:16])=O)([CH3:4])([CH3:3])[CH3:2].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.[NH2:54][C:55]1[CH:79]=[CH:78][C:77]([N:80]2[CH2:85][CH2:84][CH2:83][CH2:82][CH2:81]2)=[CH:76][C:56]=1[C:57]([NH:59][C:60]1[CH:65]=[N:64][C:63]([C:66]2[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:75])([F:74])[F:73])[CH:67]=2)=[CH:62][N:61]=1)=[O:58]>CN(C)C=O.C(OCC)(=O)C>[N:80]1([C:77]2[CH:78]=[CH:79][C:55]([NH:54][C:14]([C:13]3[CH:12]=[C:11]([CH:19]=[CH:18][CH:17]=3)[CH2:10][S:9][CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:20])=[O:16])=[C:56]([C:57](=[O:58])[NH:59][C:60]3[CH:65]=[N:64][C:63]([C:66]4[CH:71]=[CH:70][CH:69]=[C:68]([C:72]([F:73])([F:74])[F:75])[CH:67]=4)=[CH:62][N:61]=3)[CH:76]=2)[CH2:81][CH2:82][CH2:83][CH2:84][CH2:85]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 665867133-((3-Tert-butoxy-3-oxopropylthio)methyl)benzoic acidHCID 665868902-amino-5-(piperidin-1-yl)-N-(5-(3-(trifluoromethyl)phenyl)-pyrazin-2-yl)benzamide

Product 1

HCID 66586944Tert-butyl 3-(3-((4-(piperidin-1-yl)-2-((5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)carbamoyl)phenyl)carbamoyl)benzylthio)propanoateYield 108.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

To 3-((3-tert-butoxy-3-oxopropylthio)methyl)benzoic acid (53.7 mg, 0.18 mmol, 0.80 equiv) in N,N-dimethylformamide (2 mL) was added HATU (172.3 mg, 0.45 mmol, 2.00 equiv) and DIEA (117.0 mg, 0.91 mmol, 4.00 equiv) followed by the dropwise addition of a solution of 2-amino-5-(piperidin-1-yl)-N-(5-(3-(trifluoromethyl)phenyl)pyrazin-2-yl)benzamide 6d (100 mg, 0.23 mmol, 1.00 equiv) in N,N-dimethylformamide (1 mL). The resulting solution was stirred for 4 h at 25° C. in an oil bath. The resulting solution was diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 1×20 mL of water and 3×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum to yield 140 mg of crude product as a brown solid.

Workup

  1. washThe resulting mixture was washed with 1×20 mL of water and 3×20 mL of brine
  2. dry with materialThe mixture was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-2400eb3c5d8f43f2b1aa564b85d8c4d5
Source dataset
uspto-grants-2014_08
Patent number
US08809339B2

Reaction notes

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