Diisopropylethylamine → HCID 57750361、化合物

温度

50 °C

O-(7-Azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.044 g, 0.12 mmol) was added to 4-(tert-butoxycarbonylamino)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxylic acid (Intermediate 1) (0.040 g, 0.11 mmol) and N,N-diisopropylethylamine (0.023 mL, 0.13 mmol) in NMP (5 mL) at 22° C. The resulting suspension was stirred at 50° C. for 10 minutes. The mixture was cooled to ambient temperature and 1-(4-chlorophenyl)-N3,N3-dimethylpropane-1,3-diamine (Intermediate 33) (0.023 g, 0.11 mmol) was added as a solution in NMP (2 mL). The mixture was stirred at 22° C. for 3 days. The mixture was diluted with methanol and purified by ion exchange chromatography using an SCX column; the desired product was eluted from the column using 30% (2M NH3 in MeOH) in DCM and product-containing fractions were evaporated to dryness. The crude product was purified by flash silica chromatography, elution gradient 2 to 6% (10:1 MeOH/conc. NH3 (aq)) in DCM. Pure fractions were evaporated to dryness to afford tert-butyl 4-(1-(4-chlorophenyl)-3-(dimethylamino)propylcarbamoyl)-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidin-4-ylcarbamate (0.047 g, 76%) as a white solid.

1. temperatureThe mixture was cooled to ambient temperature
2. stirringThe mixture was stirred at 22° C. for 3 days
3. custompurified by ion exchange chromatography
4. washthe desired product was eluted from the column
5. additionproduct-containing fractions
6. customwere evaporated to dryness
7. customThe crude product was purified by flash silica chromatography, elution gradient 2 to 6% (10:1 MeOH/conc. NH3 (aq)) in DCM
8. customPure fractions were evaporated to dryness

ORDレコード

ord-cee351e9c2e04bfa9af38af390dddc05

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08101623B2