Diisopropylethylamine → HCID 86675611, compound

HRID 245262Notes

Reaction equation

HRID 245262 reaction equation
C(N(CC)C(C)C)(C)C.[F:10][C:11]([F:21])([F:20])[C@H:12]([NH2:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.CCCP(=O)=O.[CH2:28]([S:30]([C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][C:42]=1[O:43][CH3:44])[N:39]=[C:38]([C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:54])([F:53])[F:52])[CH:46]=1)[C:37]([CH2:55][N:56]1[CH2:61][CH2:60][CH:59]([N:62]3[CH2:66][CH2:65][CH2:64][CH2:63]3)[CH2:58][CH2:57]1)=[C:36]2[C:67](O)=[O:68])(=[O:32])=[O:31])[CH3:29]>C(OCC)(=O)C.ClCCl.C([O-])([O-])=O.[Na+].[Na+]>[CH2:28]([S:30]([C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][C:42]=1[O:43][CH3:44])[N:39]=[C:38]([C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([C:51]([F:53])([F:54])[F:52])[CH:46]=1)[C:37]([CH2:55][N:56]1[CH2:61][CH2:60][CH:59]([N:62]3[CH2:66][CH2:65][CH2:64][CH2:63]3)[CH2:58][CH2:57]1)=[C:36]2[C:67]([NH:19][C@H:12]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:11]([F:20])([F:21])[F:10])=[O:68])(=[O:31])=[O:32])[CH3:29]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamineHCID 16167369Propylphosphoric anhydrideHCID 67383517HCID 67383517, compound

Product 1

HCID 86675611HCID 86675611, compoundYield 54%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

N,N-Diisopropylethylamine (0.087 mL, 0.495 mmol), [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.045 g, 0.215 mmol), and propylphosphonic anhydride (0.126 mL of a 50% solution in ethyl acetate, 0.215 mmol) were added to a suspension of 6-(ethylsulfonyl)-7-(methyloxy)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.100 g, 0.165 mmol) in dichloromethane (2.54 mL). The mixture was stirred for 15 h, diluted with 10% Na2CO3 (2 mL) and methylene chloride (5 mL), and poured into a hydrophobic frit to separate the phases. The organic phase was absorbed onto florisil and purified via column chromatography (ISCO, 1-10% methanol/methylene chloride). The material was dissolved in methylene chloride, and the organic phase was washed with 10% Na2CO3 (2×10 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford 6-(ethylsulfonyl)-7-(methyloxy)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide as a light orange solid (0.068 g, 51% yield). MS (m/z) 763.2 (M+H+).

Workup

  1. additionpoured into a hydrophobic frit
  2. customto separate the phases
  3. customThe organic phase was absorbed onto florisil
  4. custompurified via column chromatography (ISCO, 1-10% methanol/methylene chloride)
  5. dissolutionThe material was dissolved in methylene chloride
  6. washthe organic phase was washed with 10% Na2CO3 (2×10 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-12e96580ebf24228bae3e4268a438c3b
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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