Cesium carbonate → N-(2-(1-hydroxycyclopentyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide

HRID 1502409노트

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HRID 1502409 반응식
Cl[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][N:11]=1)[N:8]=[C:7]([C:12]1([OH:17])[CH2:16][CH2:15][CH2:14][CH2:13]1)[CH:6]=[CH:5]2.[CH:18]1([C:21]([NH2:23])=[O:22])[CH2:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C(OCC)(=O)C>[OH:17][C:12]1([C:7]2[CH:6]=[CH:5][C:4]3[C:9](=[CH:10][N:11]=[C:2]([NH:23][C:21]([CH:18]4[CH2:20][CH2:19]4)=[O:22])[CH:3]=3)[N:8]=2)[CH2:16][CH2:15][CH2:14][CH2:13]1

참가 물질

6

반응물 3

HCID 10796Cesium carbonateHCID 80376CyclopropanecarboxamideHCID 866749671-(6-Chloro-1,7-naphthyridin-2-yl)cyclopentanol

생성물 1

HCID 57523996N-(2-(1-hydroxycyclopentyl)-1,7-naphthyridin-6-yl)cyclopropanecarboxamide수율 45.3%

시약·촉매·용매 2

HCID 8857Ethyl Acetate용매HCID 312751,4-Dioxane용매

반응 조건

온도
90 °C

실험 절차

A mixture of 1-(6-chloro-1,7-naphthyridin-2-yl)cyclopentanol (65 mg, 0.26 mmol), cyclopropanecarboxamide (67 mg, 0.8 mmol), Chloro[2-(dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-1-pr-1,1′-biphenyl)][2-(2-aminoethyl )Ph]Pd(II) (31 mg, 0.04 mmol), (dicyclohexylphosphino)-3-,6-dimethoxy-2,4′-6′-tri-i-pr-1,1′-biphenyl (21 mg, 0.04 mmol), and cesium carbonate (170 mg, 0.52 mmol) in 1,4-dioxane (1.5 mL) was heated at 90° C. for 1 hour. The cooled reaction mixture was diluted with ethyl acetate (50 mL) and washed with water (50 mL). The organic layer was separated, dried over sodium sulfate, filtered, and evaporated in vacuo to afford a residue that was purified by by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min) to afford the title compound as an off-white solid (35 mg, 45%). 1H NMR (400 MHz, DMSO) δ 10.97 (s, 1H), 9.12 (s, 1H), 8.47 (s, 1H), 8.30 (d, J=8.8 Hz, 1H), 8.00 (d, J=8.8 Hz, 1H), 5.32 (s, 1H), 2.29-2.17 (m, 2H), 2.11-2.03 (m, 1H), 1.95-1.75 (m, 6H), 0.91-0.78 (m, 4H). LCMS (Method E): RT=3.811 min, M+H+=298.1.

후처리

  1. customThe cooled reaction mixture
  2. washwashed with water (50 mL)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated in vacuo
  7. customto afford a residue that
  8. customwas purified by by reverse phase HPLC (5-85% acetonitrile in water with 0.1% formic acid over 14 min)

출처 및 근거

ORD 기록
ord-4d630b76231840dea0db9695bca94a91
출처 데이터셋
uspto-grants-2015_12
특허 번호
US09206175B2

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