Diisopropylethylamine → 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide

HRID 245209ノート

反応式

HRID 245209 の反応式
C(P1(=O)OP(CCC)(=O)OP(CCC)(=O)O1)CC.[CH2:19]([O:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([C:55]([OH:57])=O)=[C:27]([CH2:42][N:43]3[CH2:48][CH2:47][CH:46]([N:49]4[CH2:54][CH2:53][O:52][CH2:51][CH2:50]4)[CH2:45][CH2:44]3)[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=3)=[N:29]2)=[CH:24][C:23]=1[S:58]([CH:61]([CH3:63])[CH3:62])(=[O:60])=[O:59])[CH3:20].[F:64][C:65]([F:75])([F:74])[C@H:66]([NH2:73])[C:67]1[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=1.C(N(CC)C(C)C)(C)C>C(OCC)(=O)C.ClCCl.C(=O)(O)[O-].[Na+]>[CH2:19]([O:21][C:22]1[CH:31]=[C:30]2[C:25]([C:26]([C:55]([NH:73][C@H:66]([C:67]3[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=3)[C:65]([F:64])([F:74])[F:75])=[O:57])=[C:27]([CH2:42][N:43]3[CH2:44][CH2:45][CH:46]([N:49]4[CH2:54][CH2:53][O:52][CH2:51][CH2:50]4)[CH2:47][CH2:48]3)[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([C:38]([F:41])([F:40])[F:39])[CH:33]=3)=[N:29]2)=[CH:24][C:23]=1[S:58]([CH:61]([CH3:63])[CH3:62])(=[O:59])=[O:60])[CH3:20]

参加物

8

反応物 4

HCID 81531DiisopropylethylamineHCID 111923Propylphosphonic anhydrideHCID 11789718(alphaR)-alpha-(Trifluoromethyl)benzenemethanamineHCID 674183257-(Ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

生成物 1

HCID 534764457-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide収率 36.2%

試薬・触媒・溶媒 3

HCID 6344Dichloromethane溶媒HCID 8857Ethyl Acetate溶媒HCID 516892Sodium Bicarbonate溶媒

実験手順

T3P in ethyl acetate (1.273 mL of a 50% solution, 2.001 mmol) was added to a stirred solution of 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (1 g, 1.539 mmol), [(1R)-2,2,2-trifluoro-1-phenylethyl]amine (0.391 g, 1.847 mmol), and N,N-diisopropylethylamine (0.538 mL, 3.08 mmol) in dichloromethane (10 mL). The reaction mixture was stirred for 16 h, diluted with saturated aqueous sodium bicarbonate, and extracted with methylene chloride (three times). The combined organic extracts were washed with saturated sodium bicarbonate, brine, dried, and concentrated in vacuo. The residue was purified via column chromatography (ISCO, 0-5% methanol/methylene chloride) to afford 7-(ethyloxy)-6-[(1-methylethyl)sulfonyl]-3-{[4-(4-morpholinyl)-1-piperidinyl]methyl}-2-[3-(trifluoromethyl)phenyl]-N-[(1R)-2,2,2-trifluoro-1-phenylethyl]-4-quinolinecarboxamide (0.450 g, 34% yield) as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ10.00 (br. s., 1H), 8.48 (br. s., 1H), 7.97 (s, 1H), 7.86 (d, J=7.55 Hz, 2H), 7.71-7.78 (m, 2H), 7.60-7.68 (m, 2H), 7.42-7.47 (m, 3H), 6.20 (quin, J=8.81 Hz, 1H), 4.39 (q, J=6.80 Hz, 2H), 3.72-3.86 (m, 1H), 3.50 (br. s., 4H), 3.44 (br. s., 1H), 3.18 (br. s., 1H), 2.39 (br. s., 1H), 2.33 (br. s., 1H), 2.26 (br. s., 4H), 2.11 (br. s., 1H), 1.68 (br. s., 2H), 1.53 (br. s., 1H), 1.44 (t, J=6.80 Hz, 3H), 1.12-1.37 (m, 7H), 0.74-0.99 (m, 2H); MS (m/z) 807.2 (M+H+).

後処理

  1. extractionextracted with methylene chloride (three times)
  2. washThe combined organic extracts were washed with saturated sodium bicarbonate, brine
  3. customdried
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified via column chromatography (ISCO, 0-5% methanol/methylene chloride)

出典と根拠

ORDレコード
ord-dbdfcc2c7ee244bcb3033b9beb9fdd18
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

反応ノート

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