Diisobutylaluminum hydride → 6-(Hydroxymethyl)-5-methyl-4-[(4-phenoxyphenyl)amino]pyrrolo[1,2-b]pyridazine-3-carbonitrile

温度

-78 °C

To a solution of compound 3A (41 mg, 0.10 mmol) in THF (2 mL) at −78° C. was added DIBAL-H (1.5 M in toluene, 0.13 mL, 0.20 mmol). The reaction mixture was stirred for 6 h at −78° C., warmed to 0° C. and stirred for an additional 2h. The reaction mixture was quenched by the addition of methanol (3 mL) and sat. aq. Na2CO3 (3 mL) and then poured onto dichloromethane (20 mL). The layers were separated, the aqueous phase was extracted with dichloromethane (2×15 mL), and the combined organic extracts were dried over MgSO4, filtered, and concentrated in vacuo. Purification via preparative HPLC (YMC S5 ODS 20-100 mm, eluting with 30-100% aqueous methanol over 15 min containing 0.1% TFA, 20 mL/min) afforded 33 mg (90% yield) of compound 3B as a yellow solid. HPLC: 100% at 3.98 min (retention time) (YMC S5 ODS column, 4.6×50 mm, eluting with 10-90% aqueous methanol over 4 min containing 0.2% phosphoric acid, 4 mL/min, monitoring at 220 nm). MS (ES): m/z 371.19 [M+H]+.

1. temperaturewarmed to 0° C.
2. stirringstirred for an additional 2h
3. customThe reaction mixture was quenched by the addition of methanol (3 mL) and sat. aq. Na2CO3 (3 mL)
4. additionpoured onto dichloromethane (20 mL)
5. customThe layers were separated
6. extractionthe aqueous phase was extracted with dichloromethane (2×15 mL)
7. dry with materialthe combined organic extracts were dried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated in vacuo
10. customPurification
11. washvia preparative HPLC (YMC S5 ODS 20-100 mm, eluting with 30-100% aqueous methanol over 15 min containing 0.1% TFA, 20 mL/min)

ORDレコード

ord-c7de7ee1a6fd46dca190693ff0bbb9db

出典データセット

uspto-grants-2006_04

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07030112B2