2-Bromoethyl methyl ether → 4-(6-butyl-5-{4-cyclohexyloxy-3-[1-(2-methoxy-ethyl)-1H-pyrazol-4-yl]-phenyl}-pyridazin-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester

HRID 402037노트

반응식

HRID 402037 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:15]2[N:16]=[N:17][C:18]([CH2:39][CH2:40][CH2:41][CH3:42])=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[C:23]([C:34]4[CH:35]=[N:36][NH:37][CH:38]=4)[CH:22]=3)[CH:20]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CC(C)([O-])C.[K+].Br[CH2:50][CH2:51][O:52][CH3:53]>C1COCC1>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][CH:11]([O:14][C:15]2[N:16]=[N:17][C:18]([CH2:39][CH2:40][CH2:41][CH3:42])=[C:19]([C:21]3[CH:26]=[CH:25][C:24]([O:27][CH:28]4[CH2:33][CH2:32][CH2:31][CH2:30][CH2:29]4)=[C:23]([C:34]4[CH:38]=[N:37][N:36]([CH2:50][CH2:51][O:52][CH3:53])[CH:35]=4)[CH:22]=3)[CH:20]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

참가 물질

5

반응물 3

HCID 809722-Bromoethyl methyl ether2회HCID 23665647Potassium tert-butoxide2회HCID 673731874-{6-butyl-5-[4-cyclohexyloxy-3-(1H-pyrazol-4-yl)-phenyl]-pyridazin-3-yloxy}-piperidine-1-carboxylic acid tert-butyl ester

생성물 1

HCID 673741544-(6-butyl-5-{4-cyclohexyloxy-3-[1-(2-methoxy-ethyl)-1H-pyrazol-4-yl]-phenyl}-pyridazin-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester수율 67.1%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 4-{6-butyl-5-[4-cyclohexyloxy-3-(1H-pyrazol-4-yl)-phenyl]-pyridazin-3-yloxy}-piperidine-1-carboxylic acid tert-butyl ester (0.14 mmol, 80.6 mg), potassium tert-butoxide (0.15 mmol, 17.2 mg, 98%) and THF (1 mL) was stirred at room temperature for 40 min. 1-Bromo-2-methoxy-ethane (0.17 mmol, 0.016 mL) was added and it was stirred for 2.5 h. More potassium tert-butoxide (0.30 mmol, 34.4 mg, 98%) was added and after stirring for 30 min, more 1-bromo-2-methoxy-ethane (0.34 mmol, 0.032 mL) was added. It was stirred overnight. The reaction mixture was partitioned between ethyl acetate (10 mL) and saturated aq. sodium bicarbonate solution (10 mL). The ethyl acetate layer was dried over sodium sulfate. Purification by column chromatography on silica gel using 20-100% ethyl acetate in hexanes to provide 4-(6-butyl-5-{4-cyclohexyloxy-3-[1-(2-methoxy-ethyl)-1H-pyrazol-4-yl]-phenyl}-pyridazin-3-yloxy)-piperidine-1-carboxylic acid tert-butyl ester as colorless solid (59.5 mg).

후처리

  1. stirringit was stirred for 2.5 h
  2. stirringafter stirring for 30 min
  3. stirringIt was stirred overnight
  4. customThe reaction mixture was partitioned between ethyl acetate (10 mL) and saturated aq. sodium bicarbonate solution (10 mL)
  5. dry with materialThe ethyl acetate layer was dried over sodium sulfate
  6. customPurification by column chromatography on silica gel using 20-100% ethyl acetate in hexanes

출처 및 근거

ORD 기록
ord-80fb4c09c2b74028b66a824f76c440f0
출처 데이터셋
uspto-grants-2014_06
특허 번호
US08741900B2

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