Ethyl Acetate → HCID 117672588, compound

HRID 712614Notes

Reaction equation

HRID 712614 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[N:10][CH:11]=1)[N:8]([C:12]([NH2:14])=[O:13])[CH2:7][CH2:6][CH2:5]2.[C:15]([O:19][C:20](=[O:38])[NH:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27](B2OC(C)(C)C(C)(C)O2)[CH:28]=1)([CH3:18])([CH3:17])[CH3:16].C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>O1CCOCC1.O>[C:15]([O:19][C:20](=[O:38])[NH:21][CH2:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([C:2]2[CH:11]=[N:10][C:9]3[N:8]([C:12](=[O:13])[NH2:14])[CH2:7][CH2:6][CH2:5][C:4]=3[CH:3]=2)[CH:28]=1)([CH3:18])([CH3:16])[CH3:17]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 46739732tert-Butyl {[5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-3-yl]methyl}carbamateHCID 117667602HCID 117667602, compound

Product 1

HCID 117672588HCID 117672588, compoundYield 94.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-Bromo-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid amide (79 mg, 0.31 mmol), [5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridin-3-ylmethyl]-carbamic acid tert-butyl ester (205 mg, 0.61 mmol) and 2.0 M Na2CO3 aqueous solution (0.31 mL, 0.61 mmol) are dissolved in 2.0 mL of 1,4-dioxane. Argon gas is bubbled through the solution for 5 min. Then PdCl2dppf (16 mg, 0.021 mmol) is added. The mixture is heated at 100° C. for 2 hrs and the mixture is cooled down to room temperature. Then 30 mL of EtOAc and 20 mL of water are added and the organic layer is separated. The aqueous layer is extracted with EtOAc (2×20 mL). The organic layers are combined, dried and concentrated to give the crude product. Purification by flash column chromatography affords 112 mg of [5-(8-carbamoyl-5,6,7,8-tetrahydro-[1,8]naphthyridin-3-yl)-pyridin-3-ylmethyl]-carbamic acid tert-butyl ester

Workup

  1. customArgon gas is bubbled through the solution for 5 min
  2. temperaturethe mixture is cooled down to room temperature
  3. customthe organic layer is separated
  4. extractionThe aqueous layer is extracted with EtOAc (2×20 mL)
  5. customdried
  6. concentrationconcentrated
  7. customto give the crude product
  8. customPurification by flash column chromatography

Sources & evidence

ORD record
ord-8d3649eda5974c089677693c91ea40f8
Source dataset
uspto-grants-2015_11
Patent number
US09181272B2

Reaction notes

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