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Boron tribromide → 5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol

HRID 1027196
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HRID 1027196 반응식
C[O:2][C:3]1[CH:8]=[C:7]([N:9]2[CH:13]=[CH:12][CH:11]=[N:10]2)[CH:6]=[CH:5][C:4]=1[C:14]1[N:19]=[N:18][C:17]([C:20]2[CH2:25][CH2:24][N:23](C(OC(C)(C)C)=O)[CH2:22][CH:21]=2)=[CH:16][CH:15]=1.B(Br)(Br)Br>C(Cl)Cl>[N:9]1([C:7]2[CH:6]=[CH:5][C:4]([C:14]3[N:19]=[N:18][C:17]([C:20]4[CH2:25][CH2:24][NH:23][CH2:22][CH:21]=4)=[CH:16][CH:15]=3)=[C:3]([OH:2])[CH:8]=2)[CH:13]=[CH:12][CH:11]=[N:10]1
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4

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HCID 25134Boron tribromideHCID 86710593tert-Butyl 4-(6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)pyridazin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate

생성물 1

HCID 1363771455-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol수율 25%

시약·촉매·용매 1

HCID 6344Dichloromethane용매2회

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온도
-78 °C

실험 절차

tert-Butyl 4-(6-(2-methoxy-4-(1H-pyrazol-1-yl)phenyl)pyridazin-3-yl)-5,6-dihydropyridine-1(2H)-carboxylate (50 mg, 0.12 mmol) was dissolved in DCM (0.6 mL). The solution was cooled to −78° C. and 1 M BBr3 in DCM (0.6 mL) was added dropwise. The resulting suspension was removed from the ice bath and stirred at RT overnight. The reaction was quenched with water, diluted with MeOH then adsorbed onto a MeOH conditioned SCX column. The column was washed several times (5-7 column volumes) with MeOH then eluted with 2 N NH3 in MeOH to provide the desired product, 5-(1H-pyrazol-1-yl)-2-(6-(1,2,3,6-tetrahydropyridin-4-yl)pyridazin-3-yl)phenol, (9.7 mg, 0.03 mmol, 25% yield). LCMS Rt=0.49 min, M+1=320.1 (LCMS method Q). 1H NMR (DMSO-d6) δ 8.64 (d, J=2.3 Hz, 1H), 8.52 (d, J=9.5 Hz, 1H), 8.19 (dd, J=9.0, 3.0 Hz, 2H), 7.80 (d, J=1.3 Hz, 1H), 7.43-7.61 (m, 2H), 6.89-7.03 (m, 1H), 6.52-6.66 (m, 1H), 3.56-3.73 (m, 2H), 3.02-3.15 (m, 2H), 2.66-2.74 (m, 2H).

후처리

  1. customThe resulting suspension was removed from the ice bath
  2. customThe reaction was quenched with water
  3. additiondiluted with MeOH
  4. washThe column was washed several times (5-7 column volumes) with MeOH
  5. washthen eluted with 2 N NH3 in MeOH

출처 및 근거

ORD 기록
ord-5d604b8c7d834554b05446731d82d332
출처 데이터셋
uspto-grants-2014_05
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08729263B2

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