Chloroform → HCID 59340098, compound

HRID 905909Notes

Reaction equation

HRID 905909 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([OH:25])=[C:7]([C:14]([NH:16][CH2:17][C:18]([O:20]C(C)(C)C)=[O:19])=[O:15])[C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][CH:3]=1.C(Cl)(Cl)Cl.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[NH:64]1[CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]1.CC(C)([O-])C.[Na+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:25][C:6]1[C:5]2[C:10](=[CH:11][C:2]([N:64]3[CH2:69][CH2:68][CH2:67][CH2:66][CH2:65]3)=[CH:3][CH:4]=2)[N:9]([CH3:12])[C:8](=[O:13])[C:7]=1[C:14]([NH:16][CH2:17][C:18]([OH:20])=[O:19])=[O:15]

Participants

8

Reactant 5

HCID 6212ChloroformHCID 8082PiperidineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 23676156Sodium t-butoxideHCID 59340091HCID 59340091, compound

Product 1

HCID 59340098HCID 59340098, compoundYield 46%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A solution of tert-butyl 2-(7-bromo-4-hydroxy-1-methyl-2-oxo-1,2-dihydroquinoline-3-carboxamido)acetate (205 mg, 498 mop, Pd2dba3.CHCl3 (52 mg, 50 μmol), X-Phos (48 mg, 100 μmol) and piperidine (123 μl, 1246 μmol) in 1,4-dioxane (5 ml) was treated with sodium tert-butoxide (192 mg, 1994 μmol). The reaction was stirred at 80° C. in a sealed tube. After 15 hours, the solution was cooled to 23° C., adsorped onto silica gel, concentrated in vacuo and purified by silica gel chromatography (eluant: 5% methanol/dichloromethane, followed by 5% methanol/dichloromethane+1% AcOH), affording an yellow solid which was 83% pure. The impure solid was purified by RP HPLC (0-100% MeCN/water+1% TFA, 10 min), affording 83 mg (46%) of the product as an yellow solid.

Workup

  1. temperaturethe solution was cooled to 23° C.
  2. concentrationconcentrated in vacuo
  3. custompurified by silica gel chromatography (eluant: 5% methanol/dichloromethane, followed by 5% methanol/dichloromethane+1% AcOH)
  4. customaffording an yellow solid which
  5. customThe impure solid was purified by RP HPLC (0-100% MeCN/water+1% TFA, 10 min)

Sources & evidence

ORD record
ord-82c05beb8b104c4d85398eaea8e155ad
Source dataset
uspto-grants-2011_09
Patent number
US08012968B2

Reaction notes

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