Dichloromethane → 1,5-Anhydro-2,3-dideoxy-3-{[(4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}-5,6,7,8-tetrahydroquinolin-2-yl)carbonyl}amino]-L-threo-pentitol

HRID 2409514Notes

Reaction equation

HRID 2409514 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([CH2:8][C:9]2[C:18]3[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=3[N:12]=[C:11]([C:19]([NH:21][C@@H:22]3[C@@H:27]([OH:28])[CH2:26][O:25][CH2:24][CH2:23]3)=[O:20])[CH:10]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:35][N:36]1[CH:40]=[C:39](B2OC(C)(C)C(C)(C)O2)[CH:38]=[N:37]1.ClCCl>C1COCC1.O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:35][N:36]1[CH:40]=[C:39]([C:2]2[N:7]=[CH:6][C:5]([CH2:8][C:9]3[C:18]4[CH2:17][CH2:16][CH2:15][CH2:14][C:13]=4[N:12]=[C:11]([C:19]([NH:21][C@@H:22]4[C@@H:27]([OH:28])[CH2:26][O:25][CH2:24][CH2:23]4)=[O:20])[CH:10]=3)=[CH:4][CH:3]=2)[CH:38]=[N:37]1

Participants

9

Reactant 4

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 27739871-Methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 547673451,5-anhydro-3-[({4-[(6-chloropyridin-3-yl)methyl]-5,6,7,8-tetrahydroquinolin-2-yl}carbonyl)amino]-2,3-dideoxy-L-threo-pentitol

Product 1

HCID 547675111,5-Anhydro-2,3-dideoxy-3-{[(4-{[6-(1-methyl-1H-pyrazol-4-yl)pyridine-3-yl]methyl}-5,6,7,8-tetrahydroquinolin-2-yl)carbonyl}amino]-L-threo-pentitol

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1,5-anhydro-3-[({4-[(6-chloropyridin-3-yl)methyl]-5,6,7,8-tetrahydroquinolin-2-yl}carbonyl)amino]-2,3-dideoxy-L-threo-pentitol (Example 1, 0.081 g, 0.20 mmol) in a mixture of 2 mL of THF and 0.2 mL of water under an atmosphere of nitrogen was added cesium carbonate (0.197 g, 0.605 mmol), 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.050 g, 0.24 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), 1:1 complex with dichloromethane (0.016 g, 0.020 mmol). The reaction was irradiated in a microwave reactor at 100° C. for 30 min, cooled to rt, and diluted with ethyl acetate. The mixture was filtered through celite, concentrated in vacuo, and purified via silica gel chromatography, eluting with 1-6% methanol in dichloromethane, to provide the title compound that gave a proton NMR spectra consistent with theory and a mass ion (ES+) of 448.0 for [M+H]+: 1H NMR (400 MHz, d6-DMSO) δ 8.38 (s, 1H), 8.31 (d, J=8.2 Hz, 1H), 8.25 (s, 1H), 7.97 (s, 1H), 7.62-7.54 (m, 3H), 4.03 (br s, 2H), 3.88 (s, 2H), 3.82-3.71 (m, 3H), 3.59-3.52 (m, 1H), 3.41-3.29 (m, 2H), 3.04-2.99 (m, 1H), 2.91 (br s, 2H), 2.74 (br s, 2H), 1.85 (br s, 1H), 1.80 (s, 3H), 1.65-1.55 (m, 1H), 1.11-1.07 (m, 1H).

Workup

  1. customThe reaction was irradiated in a microwave reactor at 100° C. for 30 min
  2. filtrationThe mixture was filtered through celite
  3. concentrationconcentrated in vacuo
  4. custompurified via silica gel chromatography
  5. washeluting with 1-6% methanol in dichloromethane

Sources & evidence

ORD record
ord-13c768aa0c654e9db3292f4a8d2d667f
Source dataset
uspto-grants-2014_08
Patent number
US08815902B2

Reaction notes

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