Diisopropylethylamine → Tert-butyl 3-(3-((2-(4-(((6-(trifluoromethyl)pyridin-3-yl)methyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)benzylthio)propanoate

HRID 625216Notes

Reaction equation

HRID 625216 reaction equation
[C:1]([O:5][C:6](=[O:41])[CH2:7][CH2:8][S:9][CH2:10][C:11]1[CH:12]=[C:13]([CH:38]=[CH:39][CH:40]=1)[C:14]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)=[CH:19][C:18]=1[C:29]1[CH:30]=[C:31]([CH:35]=[CH:36][N:37]=1)[C:32](O)=[O:33])=[O:15])([CH3:4])([CH3:3])[CH3:2].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C.[F:75][C:76]([F:86])([F:85])[C:77]1[N:82]=[CH:81][C:80]([CH2:83][NH2:84])=[CH:79][CH:78]=1>CN(C)C=O>[F:85][C:76]([F:75])([F:86])[C:77]1[N:82]=[CH:81][C:80]([CH2:83][NH:84][C:32]([C:31]2[CH:35]=[CH:36][N:37]=[C:29]([C:18]3[CH:19]=[C:20]([N:23]4[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]4)[CH:21]=[CH:22][C:17]=3[NH:16][C:14]([C:13]3[CH:12]=[C:11]([CH:40]=[CH:39][CH:38]=3)[CH2:10][S:9][CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:4])[CH3:3])=[O:41])=[O:15])[CH:30]=2)=[O:33])=[CH:79][CH:78]=1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27377185-(Aminomethyl)-2-(trifluoromethyl)pyridineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 665867222-(2-(3-((3-Tert-butoxy-3-oxopropylthio)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinic acid

Product 1

HCID 66586747Tert-butyl 3-(3-((2-(4-(((6-(trifluoromethyl)pyridin-3-yl)methyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)benzylthio)propanoateYield 97.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Into a 8-mL sealed tube, was placed a solution of 2-(2-(3-((3-tert-butoxy-3-oxopropylthio)methyl)benzamido)-5-(piperidin-1-yl)phenyl)isonicotinic acid 1.1j (90 mg, 0.16 mmol, 1.00 equiv) in N,N-dimethylformamide (2 mL), HATU (90 mg, 0.24 mmol, 1.51 equiv), N,N-diisopropylethylamine (30.6 mg, 0.24 mmol, 1.52 equiv), and (6-(trifluoromethyl)pyridin-3-yl)methanamine (54 mg, 0.31 mmol, 1.96 equiv). The resulting solution was stirred overnight at room temperature. The resulting mixture was concentrated under vacuum. The residue was dissolved in ethyl acetate. The resulting mixture was washed with water and brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum to yield 114.7 mg (crude) of tert-butyl 3-(3-((2-(4-(((6-(trifluoromethyl)pyridin-3-yl)methyl)carbamoyl)pyridin-2-yl)-4-(piperidin-1-yl)phenyl)carbamoyl)benzylthio)propanoate as red oil.

Workup

  1. customInto a 8-mL sealed tube
  2. concentrationThe resulting mixture was concentrated under vacuum
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washThe resulting mixture was washed with water and brine
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-759629aa866c43c88d2b24ad08c0056b
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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