Triethylamine → (R)-(4-(1-chloropyrido[3,4-d]pyridazin-4-yl)-3-methylpiperazin-1-yl)(4,4-difluorocyclohexyl)methanone

온도

55 °C

4,4-difluorocyclohexanecarboxylic acid (277 mg, 169 mmol) and bis(2-oxo-3-oxazolidinyl)phosphinic chloride (411 mg, 1.61 mmol) were stirred in DMF (3 ml) and triethylamine (0.4 ml) for 2 minutes. The solution was added to (R)-1-chloro-4-(2-methylpiperazin-1-yl)pyrido[3,4-d]pyridazine 59 (387 mg, 1.47 mmol) and washed in with an additional 1 ml DMF. The reaction was heated at 55° C. for 1.5 hours and then stirred at RT for 17 hours. The reaction was added to saturated NaHCO3 (80 ml) and extracted three times with dichloromethane (50 ml). The combined organics were dried (MgSO4) and evaporated to give a yellow solid. The residue was chromatographed over silica with a gradient of hexane and 0-100% ethyl acetate to give (R)-(4-(1-chloropyrido[3,4-d]pyridazin-4-yl)-3-methylpiperazin-1-yl)(4,4-difluorocyclohexyl)methanone 60 as a yellow solid, 236 mg. LC/MS m/z=410 (M+H+).

1. washwashed in with an additional 1 ml DMF
2. additionThe reaction was added to saturated NaHCO3 (80 ml)
3. extractionextracted three times with dichloromethane (50 ml)
4. dry with materialThe combined organics were dried (MgSO4)
5. customevaporated
6. customto give a yellow solid
7. customThe residue was chromatographed over silica with a gradient of hexane and 0-100% ethyl acetate

ORD 기록

ord-3b739176d1b6499d86485bc8ba11eb19

출처 데이터셋

uspto-grants-2012_07

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08222251B2