Tetrahydrofuran → [4-(4-Amino-isoquinolin-1-yloxy)-piperidin-1-yl]-(1-methyl-cyclopropyl)-methanone

HRID 729609Notes

Reaction equation

HRID 729609 reaction equation
[CH3:1][C:2]1([C:5]([N:7]2[CH2:12][CH2:11][CH:10]([O:13][C:14]3[C:23]4[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=4)[C:17]([N+:24]([O-])=O)=[CH:16][N:15]=3)[CH2:9][CH2:8]2)=[O:6])[CH2:4][CH2:3]1.C1COCC1.[H][H]>[Pd]>[NH2:24][C:17]1[C:18]2[C:23](=[CH:22][CH:21]=[CH:20][CH:19]=2)[C:14]([O:13][CH:10]2[CH2:11][CH2:12][N:7]([C:5]([C:2]3([CH3:1])[CH2:4][CH2:3]3)=[O:6])[CH2:8][CH2:9]2)=[N:15][CH:16]=1

Participants

5

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 69056099(1-Methyl-cyclopropyl)-[4-(4-nitro-isoquinolin-1-yloxy)-piperidin-1-yl]-methanoneHCID 178418361HCID 178418361, compound2×

Product 1

HCID 57832814[4-(4-Amino-isoquinolin-1-yloxy)-piperidin-1-yl]-(1-methyl-cyclopropyl)-methanone

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Conditions

Temperature
40 °C

Procedure

Charge a 3 gallon autoclave with (1-methyl-cyclopropyl)-[4-(4-nitro-isoquinolin-1-yloxy)-piperidin-1-yl]-methanone (368.0 g, 1.04 moles), THF (4.42 L, 54.32 moles), and 5% Pd on carbon (dry, 40.50 g, 19.03 moles). Seal the autoclave and introduce hydrogen to 50 psi. Stir the contents at 1000 rpm at room temperature under 50 psi of hydrogen for 4.5 hours. Filter and rinse with additional THF (2.0 L, 24.58 moles). Treat the filtrate with carbon (20-40 mesh, 42.00 g) and heat to 40° C. for 1 hour. Add additional carbon (60 mesh, 47.00 g) and continue heating for 1 hour. Filter carbon through a micro fiber paper and a bed of Hyflo Super Cel® and rinse with a minimal amount of THF. Remove solvent to obtain [4-(4-amino-isoquinolin-1-yloxy)-piperidin-1-yl]-(1-methyl-cyclopropyl)-methanone, 348 g (103%) as a dark orange-red oil/foam. 1H NMR (500 MHz, CDCl3): δ 0.59 (t, J=6.0 Hz, 2H), 0.96 (t, J=6.0 Hz, 2H), 1.34 (s, 3H), 1.88-1.94 (m, 2H), 2.06-2.10 (m, 2H), 3.61-3.70 (m, 2H), 3.93-4.00 (m, 2H), 5.48-5.50 (m, 1H), 7.52 (s, 1H), 7.58 (t, J=7.0 Hz, 1H), 7.73 (t, J=7.0 Hz, 1H), 7.81 (d, J=7.0 Hz, 1H), 8.27 (d, J=8.5 Hz, 1H).

Workup

  1. customSeal the autoclave
  2. filtrationFilter
  3. additionTreat the filtrate with carbon (20-40 mesh, 42.00 g)
  4. additionAdd additional carbon (60 mesh, 47.00 g)
  5. temperaturecontinue heating for 1 hour
  6. washFilter carbon through a micro fiber paper and a bed of Hyflo Super Cel® and rinse with a minimal amount of THF

Sources & evidence

ORD record
ord-41b537b657734525bd7017e0a582643b
Source dataset
uspto-grants-2009_09
Patent number
US07582638B2

Reaction notes

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