Diisopropylethylamine → Methyl 3-(3-((4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzamido)-pyridin-2-yl)phenyl)carbamoyl)benzylthio)propanoate

HRID 625401Notes

Reaction equation

HRID 625401 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:14]1[CH:19]=[C:18]([NH:20][C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:31])([F:30])[F:29])[CH:23]=2)[CH:17]=[CH:16][N:15]=1.C(N(CC)C(C)C)(C)C.Cl[C:43]([C:45]1[CH:46]=[C:47]([CH:56]=[CH:57][CH:58]=1)[CH2:48][S:49][CH2:50][CH2:51][C:52]([O:54][CH3:55])=[O:53])=[O:44]>ClCCl>[N:8]1([C:5]2[CH:6]=[CH:7][C:2]([NH:1][C:43]([C:45]3[CH:46]=[C:47]([CH:56]=[CH:57][CH:58]=3)[CH2:48][S:49][CH2:50][CH2:51][C:52]([O:54][CH3:55])=[O:53])=[O:44])=[C:3]([C:14]3[CH:19]=[C:18]([NH:20][C:21](=[O:32])[C:22]4[CH:27]=[CH:26][CH:25]=[C:24]([C:28]([F:30])([F:31])[F:29])[CH:23]=4)[CH:17]=[CH:16][N:15]=3)[CH:4]=2)[CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 66586960N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamideHCID 86705202Methyl 3-(3-(chlorocarbonyl)benzylthio)propanoate

Product 1

HCID 66586866Methyl 3-(3-((4-(piperidin-1-yl)-2-(4-(3-(trifluoromethyl)benzamido)-pyridin-2-yl)phenyl)carbamoyl)benzylthio)propanoateYield 109.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Into a 50-mL round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of N-(2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl)-3-(trifluoromethyl)benzamide (100.0 mg, 0.23 mmol, 1.00 equiv) and N,N-diisopropylethylamine (0.2 mL) in dichloromethane (20 mL). This was followed by dropwise addition of a solution of methyl 3-(3-(chlorocarbonyl)benzylthio)propanoate 22d (74.0 mg, 0.27 mmol, 1.20 equiv) in dichloromethane (2.0 mL) with stirring at 0° C. The resulting solution was stirred for 2 h at room temperature. The resulting mixture was combined with the solution of the previous batch and then concentrated under vacuum. The residue was applied onto a silica gel column and eluted with dichloromethane:methanol (100˜100:1˜50:1). The product was obtained as 170 mg (70%) of a yellow solid.

Workup

  1. customInto a 50-mL round bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. stirringThe resulting solution was stirred for 2 h at room temperature
  4. concentrationconcentrated under vacuum
  5. washeluted with dichloromethane:methanol (100˜100:1˜50:1)

Sources & evidence

ORD record
ord-a6c75662fad94cb49c52ab11118d9a36
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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