Heptane → methyl 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinate

温度

100 °C

To a suspension of 2-chloro-7-cyclopentyl-N,N-dimethyl-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide (5.0 g, 17 mmol) in 1,4-dioxane (80 mL) in a sealed tube were added methyl 6-aminonicotinate (2.86 g, 1.10 eq), Pd(OAc)2 (0.096 g, 0.025 eq) and BINAP (0.532 g, 0.050 eq). N2 was bubbled through the resulting mixture for 20 min to degas and treated with Cs2CO3 (8.35 g, 1.5 eq). The reaction mixture was heated at 100° C. for 2.2 h. The reaction mixture was cooled to room temperature, treated with 100 mL of heptane and sonicated. Red precipitate was collected by filtration and suspended in 200 mL of water. After sonication, the solid was collected by filtration, rinsed with water (3×50 mL) and dried. The solid was triturated in THF to obtain tan solid methyl 6-(7-cyclopentyl-6-(dimethylcarbamoyl)-7H-pyrrolo[2,3-d]pyrimidin-2-ylamino)nicotinate (6.6 g, 94% yield). The filtrated was concentrated in vacuo and purified by column chromatography (Ethyl acetate/Heptane) to give additional product (0.4 g, 6% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (s, 1H), 8.89 (s, 1H), 8.83 (d, J=2.1 Hz, 1H), 8.44 (d, J=8.9 Hz, 1H), 8.22 (dd, J=8.9, 2.2 Hz, 1H), 6.67 (s, 1H), 4.77 (m, 1H), 3.86 (s, 3H), 3.06 (s, 6H), 2.42 (m, 2H), 2.00 (m, 4H), 1.68 (m, 2H); MS m/z 409.4 (M+H)+.

1. customN2 was bubbled through the resulting mixture for 20 min
2. customto degas
3. temperatureThe reaction mixture was cooled to room temperature
4. customsonicated
5. filtrationRed precipitate was collected by filtration
6. customAfter sonication
7. filtrationthe solid was collected by filtration
8. washrinsed with water (3×50 mL)
9. customdried
10. customThe solid was triturated in THF

ORDレコード

ord-ffa9a98ffacf4ce3bbfe9c39d96a5027

出典データセット

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08957074B2