1,2-Dichloroethane → HCID 53476908, compound

HRID 245234Notes

Reaction equation

HRID 245234 reaction equation
[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=1)[C:9]([CH2:25][N:26]1[CH2:31][CH2:30][CH:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]1)=[C:8]2[C:38]([OH:40])=O)(=[O:4])=[O:3].[C:41]1([C@@H:47]([NH2:49])[CH3:48])[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>CN(C)C=O.O1CCCC1>[CH3:1][S:2]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[N:11]=[C:10]([C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:23])([F:24])[F:22])[CH:16]=1)[C:9]([CH2:25][N:26]1[CH2:31][CH2:30][CH:29]([N:32]3[CH2:37][CH2:36][O:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]1)=[C:8]2[C:38]([NH:49][C@H:47]([C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)[CH3:48])=[O:40])(=[O:3])=[O:4]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 758181-Phenethylamine, (-)-HCID 81531DiisopropylethylamineHCID 67417500HCID 67417500, compound

Product 1

HCID 53476908HCID 53476908, compoundYield 49.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of 6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.200 g, 0.346 mmol), (1S)-1-phenylethanamine (0.063 g, 0.519 mmol), EDC (0.266 g, 1.39 mmol), HOBT (0.053 g, 0.346 mmol) and N,N-diisopropylethylamine (0.605 mL, 3.46 mmol) in N,N-dimethylformamide (2 mL) and tetrahydrofuran (2 mL) was heated to 50° C. overnight. The solvent was removed under reduced pressure, and the residue was dissolved in DMSO and purified via HPLC (Waters, Sunfire, 30×75 mm column, 50 mL/min, 20-60% MeCN/H2O with 0.1% TFA). The fractions containing the product were neutralized with saturated aqueous NaHCO3 and extracted with methylene chloride (three times). The combined organic extracts were washed with brine (two times), dried over Na2SO4, filtered, and concentrated to afford 6-(methylsulfonyl)-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-N-[(1S)-1-phenylethyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxamide (0.116 g, 47% yield). MS (m/z) 681.3 (M+H+).

Workup

  1. customThe solvent was removed under reduced pressure
  2. dissolutionthe residue was dissolved in DMSO
  3. custompurified via HPLC (Waters, Sunfire, 30×75 mm column, 50 mL/min, 20-60% MeCN/H2O with 0.1% TFA)
  4. additionThe fractions containing the product
  5. extractionextracted with methylene chloride (three times)
  6. washThe combined organic extracts were washed with brine (two times)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-a6e7bc6bc274435fba47dea58e4ed4bd
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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