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

HRID 2409825Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2409825
[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

Komponenten

6

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

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]+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-a8f468bf4276473c915ac42590a80e6c
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08815910B2

Notizen zur Reaktion

Wird geladen…