HCID 21025113, 화합물 → 6-(1-Hydroxy-1-methyl-ethyl)-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-3-carbonitrile

HRID 1796602노트

반응식

HRID 1796602 반응식
C(OC([C:6]1[C:7]([CH3:31])=[C:8]2[C:13]([NH:14][C:15]3[CH:20]=[CH:19][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:17][CH:16]=3)=[C:12]([C:28]#[N:29])[CH:11]=[N:10][N:9]2[CH:30]=1)=O)C.C[Mg+].[Br-]>C1COCC1.CCOCC>[OH:21][C:18]([C:6]1[C:7]([CH3:31])=[C:8]2[C:13]([NH:14][C:15]3[CH:16]=[CH:17][C:18]([O:21][C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=4)=[CH:19][CH:20]=3)=[C:12]([C:28]#[N:29])[CH:11]=[N:10][N:9]2[CH:30]=1)([CH3:19])[CH3:17]

참가 물질

5

반응물 2

HCID 21025113HCID 21025113, 화합물HCID 178418689HCID 178418689, 화합물

생성물 1

HCID 221796836-(1-Hydroxy-1-methyl-ethyl)-5-methyl-4-(4-phenoxy-phenylamino)-pyrrolo[1,2-b]pyridazine-3-carbonitrile수율 127.2%

시약·촉매·용매 2

HCID 3283Diethyl Ether용매HCID 8028Tetrahydrofuran용매

실험 절차

To a solution of compound 3A (124 mg, 0.30 mmol) in THF (5 mL) at 0° C. was slowly added a 3.0 M solution of MeMgBr in ether (0.40 mL, 1.20 mmol. The reaction was warmed to room temperature and then heated at 50° C. for 1 h. After cooling to room temperature, the reaction was quenched with EtOAc (20 mL) and saturated aqueous NH4Cl (20 mL) was added. The resulting two layers were separated and the organic layer washed with brine, dried over Na2SO4 and concentrated to an orange oil. This crude oil was purified by silica gel flash chromatography (eluted with 14-17% EtOAc/CH2Cl2) to give compound 145 as a yellow solid (76 mg, 64%). HPLC: 97% at 1.97 min (retention time) (Phenom-Prime S5 C18 column, 4.6×30 mm, eluting with 10-90% aqueous methanol over 2 min containing 0.1% TFA, 5 mL/min, monitoring at 220 nm). MS (ES): m/z 399 [M+H]+.

후처리

  1. temperatureheated at 50° C. for 1 h
  2. temperatureAfter cooling to room temperature
  3. customthe reaction was quenched with EtOAc (20 mL) and saturated aqueous NH4Cl (20 mL)
  4. additionwas added
  5. customThe resulting two layers were separated
  6. washthe organic layer washed with brine
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated to an orange oil
  9. customThis crude oil was purified by silica gel flash chromatography (eluted with 14-17% EtOAc/CH2Cl2)

출처 및 근거

ORD 기록
ord-1136640a3e6845f3b29c1c7065b54339
출처 데이터셋
uspto-grants-2006_04
특허 번호
US07030112B2

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