Sodium Carbonate → tert-butyl 1-(4-(8-(1-isobutyl-1H-pyrazol-4-yl)-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate

HRID 1037418Notes

Reaction equation

HRID 1037418 reaction equation
Cl[C:2]1[N:3]=[CH:4][CH:5]=[C:6]2[C:11](=[O:12])[C:10]([C:13]3[CH:18]=[CH:17][C:16]([C:19]4([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:29])([CH3:28])[CH3:27])[CH2:22][CH2:21][CH2:20]4)=[CH:15][CH:14]=3)=[C:9]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[O:8][C:7]=12.C(=O)([O-])[O-].[Na+].[Na+].[CH2:43]([N:47]1[CH:51]=[C:50](B2OC(C)(C)C(C)(C)O2)[CH:49]=[N:48]1)[CH:44]([CH3:46])[CH3:45]>O1CCOCC1.O.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].C(Cl)Cl>[CH2:43]([N:47]1[CH:51]=[C:50]([C:2]2[N:3]=[CH:4][CH:5]=[C:6]3[C:11](=[O:12])[C:10]([C:13]4[CH:14]=[CH:15][C:16]([C:19]5([NH:23][C:24](=[O:30])[O:25][C:26]([CH3:27])([CH3:28])[CH3:29])[CH2:20][CH2:21][CH2:22]5)=[CH:17][CH:18]=4)=[C:9]([C:31]4[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=4)[O:8][C:7]=23)[CH:49]=[N:48]1)[CH:44]([CH3:46])[CH3:45]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27593921-Isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 86671031tert-Butyl 1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate

Product 1

HCID 67067877tert-butyl 1-(4-(8-(1-isobutyl-1H-pyrazol-4-yl)-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamateYield 68%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

tert-Butyl 1-(4-(8-chloro-4-oxo-2-phenyl-4H-pyrano[2,3-c]pyridin-3-yl)phenyl)cyclobutylcarbamate (0.050 g, 0.1 mmol), sodium carbonate (0.032 g, 0.3 mmol) and 1-isobutyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (0.025 g, 0.100 mmol) were dissolved in dioxane (5 mL) and water (1 mL). The reaction mixture was degassed, PdCl2(dppf)-CH2Cl2 adduct (0.012 g, 0.0150 mmol) added and heated at 80° C. After 16 hours, the reaction mixture was filtered through Celite®, washed with ethyl acetate, evaporated and purified by column chromatography using 0-40% ethyl acetate in hexane to give the title compound (40 mg, 68%). LC-MS (Method I): RT=8.27 min, [M+H]+=591.

Workup

  1. customThe reaction mixture was degassed
  2. filtrationthe reaction mixture was filtered through Celite®
  3. washwashed with ethyl acetate
  4. customevaporated
  5. custompurified by column chromatography

Sources & evidence

ORD record
ord-f3c6e06ecfbd459baf66329c9021d8b0
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

Loading…