1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → Tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(bis(2-methoxyethyl)amino)phenyl)-carbamoyl)benzylthio)propanoate

HRID 1408035Notes

Reaction equation

HRID 1408035 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].CCN=C=NCCCN(C)C.Cl.[F:33][C:34]([F:68])([F:67])[C:35]1[CH:36]=[C:37]([CH:64]=[CH:65][CH:66]=1)[CH2:38][NH:39][C:40](=[O:63])[C:41]1[CH:46]=[CH:45][N:44]=[C:43]([C:47]2[CH:52]=[C:51]([N:53]([CH2:58][CH2:59][O:60][CH3:61])[CH2:54][CH2:55][O:56][CH3:57])[CH:50]=[CH:49][C:48]=2[NH2:62])[CH:42]=1>ClCCl.CN(C)C1C=CN=CC=1>[F:67][C:34]([F:33])([F:68])[C:35]1[CH:36]=[C:37]([CH:64]=[CH:65][CH:66]=1)[CH2:38][NH:39][C:40]([C:41]1[CH:46]=[CH:45][N:44]=[C:43]([C:47]2[CH:52]=[C:51]([N:53]([CH2:54][CH2:55][O:56][CH3:57])[CH2:58][CH2:59][O:60][CH3:61])[CH:50]=[CH:49][C:48]=2[NH:62][C:14]([C:13]2[CH:12]=[C:11]([CH:19]=[CH:18][CH:17]=2)[CH2:10][S:9][CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:20])=[O:16])[CH:42]=1)=[O:63]

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 665867133-((3-Tert-butoxy-3-oxopropylthio)methyl)benzoic acidHCID 66586795N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(bis(2-methoxyethyl)-amino)phenyl)isonicotinamide

Product 1

HCID 66586851Tert-butyl 3-(3-((2-(4-((3-(trifluoromethyl)benzyl)carbamoyl)pyridin-2-yl)-4-(bis(2-methoxyethyl)amino)phenyl)-carbamoyl)benzylthio)propanoateYield 64%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

Into a 10-mL vial, was placed a solution of 3-((3-tert-butoxy-3-oxopropylthio)methyl)benzoic acid (188.64 mg, 0.64 mmol, 2.00 equiv) in dichloromethane (5 mL), EDC.HCl (120.8 mg, 0.63 mmol, 1.98 equiv), 4-dimethylaminopyridine (77.6 mg, 0.64 mmol, 2.00 equiv), and N-(3-(trifluoromethyl)benzyl)-2-(2-amino-5-(bis(2-methoxyethyl)amino)phenyl)-isonicotinamide (160 mg, 0.32 mmol, 1.00 equiv). The resulting solution was stirred for 2 h at 25° C. in an oil bath. The reaction progress was monitored by LCMS. The resulting solution was diluted with 50 mL of dichloromethane, and washed with 3×50 mL of aqueous NH4Cl. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column and eluted with ethyl acetate/petroleum ether (1:5˜1). The product was obtained as 160 mg (64%) of a yellow solid.

Workup

  1. washwashed with 3×50 mL of aqueous NH4Cl
  2. dry with materialThe mixture was dried over anhydrous sodium sulfate
  3. concentrationconcentrated under vacuum
  4. washeluted with ethyl acetate/petroleum ether (1:5˜1)

Sources & evidence

ORD record
ord-213eaacd357d4b239d09865127713d35
Source dataset
uspto-grants-2014_12
Patent number
US08916569B2

Reaction notes

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