1,2-Dimethoxyethane → HCID 86696565, compound

HRID 1854847Notes

Reaction equation

HRID 1854847 reaction equation
Cl[C:2]1[CH:3]=[CH:4][N:5]2[C:10]([C:11]=1[CH3:12])=[C:9]([CH:13]1[CH2:15][CH2:14]1)[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6]2=[O:20].C(=O)([O-])[O-].[Cs+].[Cs+].CC1(C)C(C)(C)OB([C:35]2[CH:36]=[C:37]3[C:41](=[CH:42][CH:43]=2)[NH:40][N:39]=[CH:38]3)O1.COCCOC>C(Cl)Cl.O.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2].[Pd](Cl)Cl>[CH:13]1([C:9]2[CH:8]=[C:7]([C:16]([O:18][CH3:19])=[O:17])[C:6](=[O:20])[N:5]3[C:10]=2[C:11]([CH3:12])=[C:2]([C:35]2[CH:36]=[C:37]4[C:41](=[CH:42][CH:43]=2)[NH:40][N:39]=[CH:38]4)[CH:3]=[CH:4]3)[CH2:15][CH2:14]1

Participants

9

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10796Cesium carbonateHCID 177504691H-Indazole-5-boronic acid pinacol esterHCID 86696543Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-quinolizine-3-carboxylate

Product 1

HCID 86696565HCID 86696565, compoundYield 73.3%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

Methyl 8-chloro-1-cyclopropyl-9-methyl-4-oxo-4H-quinolizine-3-carboxylate (100 mg, 0.34 mmol), cesium carbonate (335 mg, 1.03 mmol) and 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole (92 mg, 0.38 mmol) were added to a mixture of 1,2-dimethoxyethane (3 mL) and water (1 mL). The mixture was degassed with argon. 1,1′-Bis-(diphenylphosphino)-ferrocene) palladium dichloride (28 mg, 0.03 mmol) was added. The reaction mixture was heated at 150° C. under argon atmosphere for 0.25 h. The reaction mixture was cooled. The mixture was diluted with CH2Cl2 (3 mL) and water was added (3 mL). The layers were separated using a phase separator and the aqueous layer was extracted with CH2Cl2 (2×5 mL). The combined organic layers were concentrated in vacuo. The crude product was purified by flash silica column chromatography (CH2Cl2:MeOH) (1:0 to 9:1) and dried in vacuo to afford the title compound as a yellow solid (93 mg, 72%). ESI-MS m/z: 374 (M+H)+.

Workup

  1. customThe mixture was degassed with argon
  2. temperatureThe reaction mixture was cooled
  3. additionwas added (3 mL)
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted with CH2Cl2 (2×5 mL)
  6. concentrationThe combined organic layers were concentrated in vacuo
  7. customThe crude product was purified by flash silica column chromatography (CH2Cl2:MeOH) (1:0 to 9:1)
  8. customdried in vacuo

Sources & evidence

ORD record
ord-8b6b4132b7534de2bda76947614fccad
Source dataset
uspto-grants-2015_02
Patent number
US08962842B2

Reaction notes

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