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Tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate → Tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 595956
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HRID 595956 반응식
[NH2:1][C:2]1[C:3]([C:18]2[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[C:20]([F:31])[CH:19]=2)=[N:4][C:5]([C:8]2[CH2:17][CH2:16][C:11]3([O:15][CH2:14][CH2:13][O:12]3)[CH2:10][CH:9]=2)=[CH:6][N:7]=1.[H][H]>C(Cl)Cl.CO.[Pd]>[NH2:1][C:2]1[C:3]([C:18]2[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:26])[CH3:27])=[O:23])=[C:20]([F:31])[CH:19]=2)=[N:4][C:5]([CH:8]2[CH2:17][CH2:16][C:11]3([O:12][CH2:13][CH2:14][O:15]3)[CH2:10][CH2:9]2)=[CH:6][N:7]=1
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HCID 118045818Tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoateHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 118045406Tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-yl)-2-fluorobenzoate수율 74.1%

시약·촉매·용매 3

HCID 23938Palladium촉매HCID 887Methanol용매
HCID 6344Dichloromethane용매

실험 절차

To a solution of tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoate (11 g, 25.7 mmol) in DCM (100 mL) and MeOH (100 mL) at room temperature was added Pd/C (5 g, 25.7 mmol) (10% in carbon, wet). The resulting mixture was vacuumed, and then refilled with hydrogen. The process was repeated three times. Then the reaction was stirred at room temperature under H2 atmosphere for 6 h. Catalyst was filtered out through Celite®, and washed with DCM. The filtrate was concentrated, and the residue was dissolved in DCM (60 mL), filtered and concentrated. The crude product was purified by flash chromatography eluting with 0-100% of EtOAc/heptane to provide tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]decan-8-yl)pyrazin-2-yl)-2-fluorobenzoate (8.18 g, 19.04 mmol, 74%) as a light yellow solid. LCMS (m/z): 430.2 (MH+), 0.99 min; 1H NMR (400 MHz, DMSO-d6) δ ppm 7.98-7.82 (m, 2H), 7.71-7.49 (m, 2H), 6.13 (s, 2H), 3.85 (s, 4H), 3.30 (s, 1H), 2.77-2.55 (m, 1H), 2.48 (dt, J=3.62, 1.91 Hz, 2H), 1.88-1.65 (m, 6H), 1.63-1.46 (m, 10H).

후처리

  1. filtrationCatalyst was filtered out through Celite®
  2. washwashed with DCM
  3. concentrationThe filtrate was concentrated
  4. dissolutionthe residue was dissolved in DCM (60 mL)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by flash chromatography
  8. washeluting with 0-100% of EtOAc/heptane

출처 및 근거

ORD 기록
ord-dfdda2b8d2ce460a829c3a537341eed3
출처 데이터셋
uspto-grants-2016_01
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US09242996B2

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