Reaktion #682592

Reaktionsgleichung

benzo[d]thiazol-6-amine

Na2CO3

xanthphos

Ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate

ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate

→

ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate

Lösungsmittel

H2O

1,4-Dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigedegassed for 10 min
2. 2
   Sonstigedegassed once again for 15 min
3. 3
   FiltrationThe reaction mass was filtered through a small pad of celite
4. 4
   Einengenconcentrated the filtrate
5. 5
   Sonstigeto remove solvent
6. 6
   SonstigeThe crude material obtained
7. 7
   Sonstigewas purified by column chromatography through silica gel and MeOH
8. 8
   SonstigeThe material obtained
9. 9
   Sonstigewas further purified by preparative TLC

Vorschrift

Ethyl 2-(6-chloro-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate (28a) (50 mg, 0.15 mmol) was dissolved in 1,4-Dioxane (5 mL): H2O (1 mL), to it benzo[d]thiazol-6-amine (0.15 mmol), Na2CO3 (0.6 mmol) and xanthphos (0.06 mmol) were added and degassed for 10 min. Pd2(dba)3 (0.06 mmol) was added and degassed once again for 15 min and heated at 115° C., overnight. The reaction mass was filtered through a small pad of celite and concentrated the filtrate to remove solvent. The crude material obtained was purified by column chromatography through silica gel and MeOH: CHCl3 as eluent. The material obtained was further purified by preparative TLC to obtain the title compound, ethyl 2-(6-(benzo[d]thiazol-6-ylamino)-4-(isopropylamino)pyridin-3-yl)-5-methyloxazole-4-carboxylate. 1H NMR: 400 MHz, DMSO-d6: δ 1.28-1.35 (m, 9H), 2.66 (s, 3H), 3.71-3.72 (m, 1H), 4.30 (q, J=7.20 Hz, 2H), 6.16 (s, 1H), 7.59 (dd, J=2.40, 9.00 Hz, 1H), 7.96 (d, J=8.80 Hz, 1H), 8.10 (d, J=7.20 Hz, 1H), 8.53 (s, 1H), 8.66 (d, J=2.00 Hz, 1H), 9.16 (s, 1H), 9.36 (s, 1H). LC/MS: Ascentis Express C18, 5×2.1 mm, 2.7 μm; Solvent A=2% ACN: 98% H2O: 10 mM NH4COOH; Solvent B=98% ACN: 2% H2O: 10 mM NH4COOH; gradient 0-100% B over 1.5 min; retention time: 2.127 min; LCMS (ES-API), m/z 438.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μL/min; Retention time: 7.483 min; Purity: 99.7%.

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