Hydrochloric Acid → 5-(2-[1-methyl-1H-imidazol-2-yl]thieno[3,2-b]pyridin-7-ylamino)-2-methylindole-1-carboxylic acid methylamide

HRID 2308090

Reaktionsgleichung

Reaktionsgleichung von HRID 2308090
[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH2:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:15])=[O:4].Cl.O1CCOCC1.Cl[C:24]1[CH:29]=[CH:28][N:27]=[C:26]2[CH:30]=[C:31]([C:33]3[N:34]([CH3:38])[CH:35]=[CH:36][N:37]=3)[S:32][C:25]=12.C([O-])(O)=O.[Na+]>CC(O)C.O.CCOC(C)=O>[CH3:1][NH:2][C:3]([N:5]1[C:13]2[C:8](=[CH:9][C:10]([NH:14][C:24]3[CH:29]=[CH:28][N:27]=[C:26]4[CH:30]=[C:31]([C:33]5[N:34]([CH3:38])[CH:35]=[CH:36][N:37]=5)[S:32][C:25]=34)=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:15])=[O:4]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 207460575-Amino-2-methylindole-1-carboxylic acid methylamideHCID 221435637-chloro-2-(1-methyl-1H-imidazol-2-yl)-thieno[3,2-b]pyridine

Produkt 1

HCID 101945545-(2-[1-methyl-1H-imidazol-2-yl]thieno[3,2-b]pyridin-7-ylamino)-2-methylindole-1-carboxylic acid methylamideAusbeute 83,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 3776IsopropanolLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a stirred slurry of 5-amino-2-methylindole-1-carboxylic acid methylamide (632 mg, 3.1 mmole), prepared in Example 1(a) step (iii), in 2-propanol (35 ml) was added 4.0 M HCl in 1,4-dioxane (0.75 ml, 3 mmole) followed by 7-chloro-2-(1-methyl-1H-imidazol-2-yl)thieno[3,2-b]pyridine (500 mg, 2 mmole), prepared as described in PCT application WO-99/24440, Example 149. The resultant solution was heated at reflux for 54 hours. After cooling to room temperature, the crude reaction mixture was poured into sat'd NaHCO3 (150 ml), then diluted with water (50 ml). The precipitate that formed was collected by filtration, then washed with water (2×50 ml) and EtOAc (3×30 ml). The solid obtained was suspended in EtOAc (15 ml), filtered and washed with Et2O (3×10 ml) to give 693 mg (83%) of a beige solid. 1H NMR (DMSO-d6): δ 8.76 (1H, s), 8.22 (1H, d, J=5.5 Hz), 8.20 (1H, q, J=5.4 Hz), 7.68 (1H, s), 7.60 (1H, d, J=8.7 Hz), 7.35 (1H, d, J=0.2 Hz), 7.34 (1H, d, J=1.9Hz), 7.08 (1H, dd, J=1.9, 8.7Hz), 6.98 (1H, d, J=0.2 Hz), 6.67 (1H, d, J=5.5Hz), 6.36 (1H, s), 3.94 (3H, s), 2.88 (3H, d, J=5.4 Hz), 2.48 (3H, s). Anal. Calcd. for C22H20N6OS.1.0H2O: C, 60.81; H, 5.10; N, 19.34; S, 7.38. Found: C, 60.53; H, 5.13; N, 19.07; S, 7.50.

Aufarbeitung

  1. customprepared
  2. temperatureat reflux for 54 hours
  3. customthe crude reaction mixture
  4. customThe precipitate that formed
  5. filtrationwas collected by filtration
  6. washwashed with water (2×50 ml) and EtOAc (3×30 ml)
  7. customThe solid obtained
  8. filtrationfiltered
  9. washwashed with Et2O (3×10 ml)

Quellen und Nachweise

ORD-Eintrag
ord-9f8132cf345b481c8382ad022149e2b8
Quelldatensatz
uspto-grants-2004_12
Patentnummer
US06833456B2

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