반응 #743765

반응 방정식

32A

(R,Z)-2-amino-7-(2-bromo-4-fluorophenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O—((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl oxime

2-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Na2CO3

TFA

→

H2O AcCN

(R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O—((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl oxime

용매

DMA

EtOAc

반응 조건

후처리

1. 1
   세척washed with H2O, brine
2. 2
   건조dried over Na2SO4
3. 3
   농축concentrated in vacuo

실험 절차

To a vial containing 32A (40 mg, 0.083 mmol), 2-methoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (58 mg, 0.25 mmol), Na2CO3 (0.5 mL, 1.0 mmol), Pd(dppf)2Cl2 (3.4 mg, 0.004 mmol) and DMA (0.5 mL) was heated to 130° C. for 20 min in the microwave. The resultant crude mixture was diluted with EtOAc, and washed with H2O, brine, dried over Na2SO4, and concentrated in vacuo to yield (R,Z)-2-amino-7-(4-fluoro-2-(6-methoxypyridin-2-yl)phenyl)-4-methyl-7,8-dihydropyrido[4,3-d]pyrimidin-5(6H)-one O—((R)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl oxime (32) after reverse-phase preparative HPLC (16 mg, 39% yield, 10-70% H2O—AcCN, 0.035% TFA). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.35 (s, 3H) 1.41 (s, 3H) 2.85 (s, 3H) 3.15 (dd, J=17.05, 10.48 Hz, 1H) 3.46 (dd, J=17.18, 3.79 Hz, 1H) 3.70-3.80 (m, 1H) 3.88 (s, 3H) 3.99-4.17 (m, 3H) 4.36-4.49 (m, 1H) 4.90 (dd, J=10.36, 3.54 Hz, 1H) 4.30-5.10 (br, 2H) 5.80 (br, 1H) 6.76 (d, J=8.34 Hz, 1H) 7.02 (d, J=7.33 Hz, 1H) 7.10-7.24 (m, 2H) 7.60 (dd, J=8.59, 5.56 Hz, 1H) 7.68 (t, J=7.83 Hz, 1H). ESI-MS: m/z 509.4 (M+H)+.

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