Binap, (A+-)- → 4-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one

HRID 530826노트

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HRID 530826 반응식
Br[C:2]1[C:3](=[O:22])[N:4]([CH3:21])[N:5]=[C:6]([O:8][CH2:9][C@H:10]2[CH2:12][C@@H:11]2[C:13]2[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][N:14]=2)[CH:7]=1.[CH2:23]([C:25]1[CH:29]=[C:28]([CH2:30][NH2:31])[N:27]([CH3:32])[N:26]=1)[CH3:24].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[CH2:23]([C:25]1[CH:29]=[C:28]([CH2:30][NH:31][C:2]2[C:3](=[O:22])[N:4]([CH3:21])[N:5]=[C:6]([O:8][CH2:9][C@H:10]3[CH2:12][C@@H:11]3[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][N:14]=3)[CH:7]=2)[N:27]([CH3:32])[N:26]=1)[CH3:24]

참가 물질

8

반응물 4

HCID 634876Binap, (A+-)-HCID 23006075(3-Ethyl-1-methyl-1H-pyrazol-5-yl)methanamineHCID 23676156Sodium t-butoxideHCID 904192134-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl) methoxy)-2-methylpyridazin-3(2H)-one

생성물 1

HCID 904544054-((3-ethyl-1-methyl-1H-pyrazol-5-yl)methylamino)-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 962Water용매HCID 1140Toluene용매

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온도
100 °C

실험 절차

To a solution of 4-bromo-6-(((1S,2S)-2-(5-methoxypyridin-2-yl)cyclopropyl)methoxy)-2-methylpyridazin-3(2H)-one (70 mg, 0.19 mmol) in toluene (5 mL) under N2, ((3-ethyl-1-methyl-1H-pyrazol-5-yl)methanamine (32.2 mg, 0.23 mmol), Pd2(dba)3 (18 mg, 0.019 mmol), BINAP (35 mg, 0.06 mmol) and NaOtBu (27 mg, 0.285 mmol) were added. After the reaction mixture was stirred at 100° C. overnight, 15 mL water was added. The mixture was extracted with EtOAc (2×10 mL). The combined organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by Prep-HPLC to give the title compound as oil. 1H NMR (400 MHz, CDCl3) δ 8.43 (s, 1H), 7.73 (d, 1H), 7.21 (d, 1H), 6.14 (s, 1H), 5.75 (s, 1H), 4.45-4.28 (m, 3H), 4.00 (d, 4H), 3.89 (s, 3H), 3.67 (s, 3H), 2.66 (d, 2H), 2.53 (s, 1H), 1.88 (s, 1H), 1.41 (s, 2H), 1.22 (t, 3H).

후처리

  1. extractionThe mixture was extracted with EtOAc (2×10 mL)
  2. dry with materialThe combined organics were dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by Prep-HPLC

출처 및 근거

ORD 기록
ord-cc22ce6dda9f43ebbf0b3ece51937e9d
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09353104B2

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