Pyridine → N1-methyl-N1-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)phenyl)isophthalamide

HRID 926848ノート

反応式

HRID 926848 の反応式
[NH2:1][C:2]1[CH:25]=[CH:24][C:23]([N:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]2)=[CH:22][C:3]=1[C:4]([NH:6][C:7]1[S:8][CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)[N:11]=1)=[O:5].N1C=CC=CC=1.[CH3:38][N:39]([CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)[C:40]([C:42]1[CH:43]=[C:44]([CH:48]=[CH:49][CH:50]=1)[C:45](Cl)=[O:46])=[O:41]>ClCCl.C(OCC)(=O)C>[CH3:38][N:39]([CH2:51][CH2:52][N:53]1[CH2:58][CH2:57][O:56][CH2:55][CH2:54]1)[C:40](=[O:41])[C:42]1[CH:50]=[CH:49][CH:48]=[C:44]([C:45]([NH:1][C:2]2[CH:25]=[CH:24][C:23]([N:26]3[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]3)=[CH:22][C:3]=2[C:4](=[O:5])[NH:6][C:7]2[S:8][CH:9]=[C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:20])([F:21])[F:19])[CH:13]=3)[N:11]=2)=[O:46])[CH:43]=1

参加物

6

反応物 3

HCID 1049PyridineHCID 867052033-(Methyl(2-morpholinoethyl)carbamoyl)benzoyl chlorideHCID 867052072-amino-5-(piperidin-1-yl)-N-(4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)benzamide

生成物 1

HCID 56643723N1-methyl-N1-(2-morpholinoethyl)-N3-(4-(piperidin-1-yl)-2-((4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)carbamoyl)phenyl)isophthalamide

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

Into a 50-mL round bottom flask, was placed a solution of 2-amino-5-(piperidin-1-yl)-N-(4-(3-(trifluoromethyl)phenyl)thiazol-2-yl)benzamide (287 mg, 0.64 mmol, 1.00 equiv) in dichloromethane (3 mL), and pyridine (406 mg, 5.13 mmol, 8.00 equiv). This was followed by dropwise addition of a solution of 3-(methyl(2-morpholinoethyl)carbamoyl)benzoyl chloride (300 mg, 0.97 mmol, 1.50 equiv) in dichloromethane (2 mL) with stirring. The resulting solution was stirred for 1 h at room temperature, then diluted with 50 mL of ethyl acetate. The resulting mixture was washed with 1×20 mL of hydrogen chloride (1 N) and 2×20 mL of brine. The mixture was dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (300 mg) was purified by reverse phase HPLC eluting with a water/CH3CN gradient containing 0.05% TFA. The product was obtained as 120 mg (20%) of as a yellow solid. 1H-NMR (300 MHz, DMSO, ppm): δ 12.89(s, 1H), 10.93(s, 1H), 9.79(s, 1H), 8.26 (m, 2H), 8.00(m, 4H), 7.69(m, 4H), 7.53(s, 1H), 7.27(d, J=8.7 Hz, 1H), 4.01(s, 2H), 3.85(s, 2H), 3.63(s, 4H), 3.44(s, 2H), 3.17(m, 6H), 2.99(s, 3H), 1.70(m, 6H). MS (ES, m/z): 721 [M+H]+.

後処理

  1. customInto a 50-mL round bottom flask, was placed
  2. stirringThe resulting solution was stirred for 1 h at room temperature
  3. washThe resulting mixture was washed with 1×20 mL of hydrogen chloride (1 N) and 2×20 mL of brine
  4. dry with materialThe mixture was dried over anhydrous sodium sulfate
  5. concentrationconcentrated under vacuum
  6. customThe crude product (300 mg) was purified by reverse phase HPLC
  7. washeluting with a water/CH3CN gradient
  8. additioncontaining 0.05% TFA
  9. customThe product was obtained as 120 mg (20%) of as a yellow solid

出典と根拠

ORDレコード
ord-164d4b63cf064fdc8432ec9d3bb314c9
出典データセット
uspto-grants-2016_03
特許番号
US09289430B2

反応ノート

読み込み中…