Hydrochloric Acid → N-[2-Methoxy-5-(3-{2-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)amino]pyrimidin-4-yl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamide

HRID 1157611Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157611
Cl[C:2]1[N:7]=[C:6]([C:8]2[C:9]([C:17]3[CH:18]=[CH:19][C:20]([O:32][CH3:33])=[C:21]([NH:23][C:24](=[O:31])[CH2:25][C:26]4[S:27][CH:28]=[CH:29][CH:30]=4)[CH:22]=3)=[N:10][N:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=23)[CH:5]=[CH:4][N:3]=1.[CH3:34][N:35]1[CH2:44][CH2:43][C:42]2[C:37](=[CH:38][C:39]([NH2:45])=[CH:40][CH:41]=2)[CH2:36]1.Cl>CC(O)C>[CH3:33][O:32][C:20]1[CH:19]=[CH:18][C:17]([C:9]2[C:8]([C:6]3[CH:5]=[CH:4][N:3]=[C:2]([NH:45][C:39]4[CH:38]=[C:37]5[C:42]([CH2:43][CH2:44][N:35]([CH3:34])[CH2:36]5)=[CH:41][CH:40]=4)[N:7]=3)=[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][N:11]3[N:10]=2)=[CH:22][C:21]=1[NH:23][C:24](=[O:31])[CH2:25][C:26]1[S:27][CH:28]=[CH:29][CH:30]=1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 129995062-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amineHCID 57737232N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide

Produkt 1

HCID 16749890N-[2-Methoxy-5-(3-{2-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)amino]pyrimidin-4-yl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamideAusbeute 53,5 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 3776IsopropanolLösungsmittel

Reaktionsbedingungen

Temperatur
180 °C

Versuchsvorschrift

To a solution of N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide (110 mg, 0.23 mmol) (see Example 48, step F) in anhydrous i-PrOH (3 mL) was added 2-methyl-1,2,3,4-tetrahydroisoquinolin-7-amine (39 mg, 0.24 mmol), followed by catalytic 12M HCl. After heating for 10 min in the microwave at 180° C., the reaction was quenched with saturated NaHCO3 (25 mL), the solvent removed by rotary evaporation, and the aqueous layer extracted with DCM (25 mL). The organic layer was concentrated and purified by column chromatography (1-10% MeOH in DCM) to provide the product (74 mg, 53%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 2.28 (s, 3H), 2.53-2.55 (m, 2H), 2.70-2.72 (m, 2H), 3.36 (s, 2H), 3.87 (s, 3H), 3.97 (s, 2H), 6.49 (d, 1H, J=5.1 Hz), 6.94-6.95 (m, 2H), 7.05-7.13 (m, 2H), 7.25-7.27 (d, 1H, J=8.1 Hz), 7.35-7.43 (m, 3H), 7.48 (s, 1H), 8.19 (d, 1H, J=5.3 Hz), 8.31 (s, 1H), 8.43 (d, 1H, J=8.6 Hz), 8.78 (d, 1H, J=6.8 Hz) 9.38 (s, 1H), 9.45 (s, 1H) ppm. ES-LC/MS m/z=602 [M+H]+.

Aufarbeitung

  1. customthe reaction was quenched with saturated NaHCO3 (25 mL)
  2. customthe solvent removed by rotary evaporation
  3. extractionthe aqueous layer extracted with DCM (25 mL)
  4. concentrationThe organic layer was concentrated
  5. custompurified by column chromatography (1-10% MeOH in DCM)

Quellen und Nachweise

ORD-Eintrag
ord-90caadda8f5e440b8b9fdc0cdc063f38
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807673B2

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