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 595956Notes

Reaction equation

HRID 595956 reaction equation
[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

Participants

6

Reactant 2

HCID 118045818Tert-butyl 4-(3-amino-6-(1,4-dioxaspiro[4.5]dec-7-en-8-yl)pyrazin-2-yl)-2-fluorobenzoateHCID 178418361HCID 178418361, compound

Product 1

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

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-dfdda2b8d2ce460a829c3a537341eed3
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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