Diisopropylethylamine → 6-(methylsulfonyl)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

HRID 245238

Reaction equation

HRID 245238 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[CH2:36][CH2:35][CH2:34][CH2:33]3)[CH2:28][CH2:27]1)=[C:8]2[C:37](O)=[O:38])(=[O:4])=[O:3].[F:40][C:41]([F:51])([F:50])[C@H:42]([NH2:49])[C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1.C(N(CC)C(C)C)(C)C.C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.CCCP(=O)=O>C(OCC)(=O)C.ClCCl.O>[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[CH2:33][CH2:34][CH2:35][CH2:36]3)[CH2:28][CH2:27]1)=[C:8]2[C:37]([NH:49][C@H:42]([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:41]([F:50])([F:51])[F:40])=[O:38])(=[O:4])=[O:3]

Participants

9

Reactant 5

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydride2×HCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamine2×HCID 16167369Propylphosphoric anhydride2×HCID 674194336-(Methylsulfonyl)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 866756096-(methylsulfonyl)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamideYield 29.9%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

A suspension of 6-(methylsulfonyl)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (0.125 g, 0.223 mmol), [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.061 g, 0.289 mmol), N,N-diisopropylethylamine (0.117 mL, 0.668 mmol), and T3P (propylphosphonic anhydride, 0.170 mL of a 50% w/v solution in ethyl acetate, 0.289 mmol) in dichloromethane (3.42 mL) was stirred at room temperature for 20 h. Additional portions of [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.031 g, 0.145 mmol) and T3P (propylphosphonic anhydride, 0.085 mL of a 50% w/v solution in ethyl acetate, 0.145 mmol) were added, and the mixture stirred for 2 h. Water (2 mL) was added, and the mixture was poured through a hydrophobic frit. The isolated organic phase was absorbed onto florisil and purified via column chromatography (ISCO, 4 g silica, 1-6% methanol/methylene chloride) to afford 6-(methylsulfonyl)-3-{[4-(1-pyrrolidinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.048 g, 28% yield). MS (m/z) 719.2 (M+H+).

Workup

  1. additionthe mixture was poured through a hydrophobic frit
  2. customThe isolated organic phase was absorbed onto florisil
  3. custompurified via column chromatography (ISCO, 4 g silica, 1-6% methanol/methylene chloride)

Sources & evidence

ORD record
ord-c1238bcc238b4d5b91a7055a57feb95f
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Linked notes

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