Hydrochloric Acid → N-{5-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide

HRID 1157610Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1157610
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]([CH3:46])[CH:36]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[C:41]([NH2:45])[CH:42]=2)[CH2:37]1.Cl>CC(O)C>[CH3:34][N:35]([CH3:46])[CH:36]1[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[C:41]([NH:45][C:2]3[N:7]=[C:6]([C:8]4[C:9]([C:17]5[CH:18]=[CH:19][C:20]([O:32][CH3:33])=[C:21]([NH:23][C:24](=[O:31])[CH2:25][C:26]6[S:27][CH:28]=[CH:29][CH:30]=6)[CH:22]=5)=[N:10][N:11]5[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=45)[CH:5]=[CH:4][N:3]=3)[CH:42]=2)[CH2:37]1

Komponenten

5

Edukt 3

HCID 313Hydrochloric AcidHCID 54309634HCID 54309634, VerbindungHCID 57737232N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide

Produkt 1

HCID 16749889N-{5-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamideAusbeute 24 %

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 (90 mg, 0.19 mmol) in anhydrous i-PrOH (3 mL) was added N2,N2-dimethylindane-2,5-diamine (37 mg, 0.21 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) and the solvent was removed by rotary evaporation. The aqueous layer was extracted with DCM (25 mL), the organic layer-concentrated, and purified by column chromatography (1-10% MeOH in DCM) to provide the product (27 mg, 24%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 2.18 (s, 6H), 2.65-2.71 (m, 2H), 2.88-2.97 (m, 2H), 3.89 (s, 3H), 3.98 (s, 2H), 6.51 (d, 1H, J=5.3 Hz), 6.94-6.96 (m, 2H), 7.02-7.14 (m, 3H), 7.26-7.28 (m, 1H), 7.35-7.43 (m, 3H), 7.63 (s, 1H), 8.20 (d, 1H, J=5.3 Hz), 8.31 (s, 1H), 8.43 (d, 1H, J=8.9 Hz), 8.79 (d, 1H, J=7.0 Hz) 9.38 (s, 1H), 9.45 (s, 1H) ppm. ES-LC/MS m/z=616 [M+H]+.

Aufarbeitung

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

Quellen und Nachweise

ORD-Eintrag
ord-f926c9a1d69341e9a6f0b36aff26391f
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807673B2

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