Pyridine → Methyl 3-(3-(2-(4-(tert-butoxycarbonyl(3-(trifluoromethyl)benzyl)amino)pyridin-2-yl)-4-(piperidin-1-yl)phenylcarbamoyl)-benzylthio)propanoate

HRID 625390Notes

Reaction equation

HRID 625390 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]([N:20]([CH2:28][C:29]2[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:38])([F:37])[F:36])[CH:30]=2)[C:21](=[O:27])[O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=[CH:16][N:15]=1.Cl[C:40]([C:42]1[CH:43]=[C:44]([CH:53]=[CH:54][CH:55]=1)[CH2:45][S:46][CH2:47][CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:41].N1C=CC=CC=1.OS(O)(=O)=O>C(Cl)Cl.C1COCC1.O>[C:23]([O:22][C:21]([N:20]([CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[C:31]([C:35]([F:37])([F:38])[F:36])[CH:30]=1)[C:18]1[CH:17]=[CH:16][N:15]=[C:14]([C:3]2[CH:4]=[C:5]([N:8]3[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]3)[CH:6]=[CH:7][C:2]=2[NH:1][C:40]([C:42]2[CH:43]=[C:44]([CH:53]=[CH:54][CH:55]=2)[CH2:45][S:46][CH2:47][CH2:48][C:49]([O:51][CH3:52])=[O:50])=[O:41])[CH:19]=1)=[O:27])([CH3:26])([CH3:24])[CH3:25]

Participants

7

Reactant 4

HCID 1049PyridineHCID 1118Sulfuric AcidHCID 66587401Tert-butyl 2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl(3-(trifluoro-methyl)benzyl)carbamateHCID 86705202Methyl 3-(3-(chlorocarbonyl)benzylthio)propanoate

Product 1

HCID 66588055Methyl 3-(3-(2-(4-(tert-butoxycarbonyl(3-(trifluoromethyl)benzyl)amino)pyridin-2-yl)-4-(piperidin-1-yl)phenylcarbamoyl)-benzylthio)propanoateYield 92%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 21919333Tetrahydrofurane dichloromethaneSolvent

Procedure

Into a 50-mL round bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of tert-butyl 2-(2-amino-5-(piperidin-1-yl)phenyl)pyridin-4-yl(3-(trifluoromethyl)benzyl)carbamate (600 mg, 1.14 mmol, 1.00 equiv) in DCM/THF (5/20 mL), methyl 3-(3-(chlorocarbonyl)benzylthio)propanoate (580 mg, 2.13 mmol, 1.40 equiv), and pyridine (750 mg, 9.49 mmol, 3.00 equiv). The resulting solution was stirred for 3 h at room temperature. The reaction progress was monitored by LCMS. The resulting solution was diluted with 30 mL of H2O and adjusted to pH 6-7 with H2SO4 (1 N). The resulting solution was extracted with 3×40 mL of dichloromethane and the organic layers combined. The resulting mixture was washed with 1×30 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum to yield 800 mg (92%) of product as a yellow oil.

Workup

  1. customInto a 50-mL round bottom flask purged
  2. temperaturemaintained with an inert atmosphere of nitrogen
  3. extractionThe resulting solution was extracted with 3×40 mL of dichloromethane
  4. washThe resulting mixture was washed with 1×30 mL of brine
  5. dry with materialThe mixture was dried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-0675909097c6491fadb0a775bcd73264
Source dataset
uspto-grants-2016_04
Patent number
US09301951B2

Reaction notes

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