Diisopropylethylamine → 4-[4-(7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ylamino)-3-methoxy-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

In a 10 mL sealed tube, to 7-Bromo-pyrrolo[2,1-f][1,2,4]triazin-2-ol (150.0 mg, 0.701 mmol) and N,N-Diisopropylethylamine (0.488 mL, 2.80 mmol) in 3.8 mL of anhydrous DMF was added N-Phenylbis(trifluoromethanesulfonimide (263 mg, 0.736 mmol). After stirring at room temperature for 2 hours, 4-(4-Amino-3-methoxy-phenyl)-piperidin-1-carboxylic acid tert-butyl ester (214.7 mg, 0.701 mmol) was added. The reaction mixture was heated at 65° C. for 4 hours. The reaction was conc. in vacuo. Water and brine were added and the contents were extracted with DCM. The combined organic layers were dried with sodium sulfate, filtered, and conc. in vacuo. The reaction mixture was purified via silica gel column chromatography using 100:1 DCM:MeOH as the eluant to afford a the title compound as a red oil (52%). 1H NMR (DMSO-d6)-8.89 (s, 1H), 8.23 (d, 1H, J=8.20 Hz), 7.83 (s, 1H), 6.98-6.95 (m, 2H), 6.91 (d, 1H, J=4.72 Hz), 6.85 (d, 1H, J=8.52 Hz), 4.66-4.55 (br s, 1H), 4.16-3.99 (m, 3H), 3.89 (s, 3H), 2.87-2.75 (m, 2H), 1.78 (d, 2H, J=12.93 Hz), 1.70 (d, 1H, J=12.57 Hz), 1.42 (s, 9H).

1. customIn a 10 mL sealed tube
2. temperatureThe reaction mixture was heated at 65° C. for 4 hours
3. extractionthe contents were extracted with DCM
4. dry with materialThe combined organic layers were dried with sodium sulfate
5. filtrationfiltered
6. customThe reaction mixture was purified via silica gel column chromatography

ORD 기록

ord-c1ca8e1bc4c4455ebde5b81242c927a4

출처 데이터셋

uspto-grants-2013_06

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08471005B2