Dichloromethane → HCID 58204357, compound

HRID 1800193Notes

Reaction equation

HRID 1800193 reaction equation
[OH:1][CH2:2][CH2:3][N:4]([CH:22]([CH3:24])[CH3:23])[C:5]([C:7]1[N:16]=[C:15]2[N:9]([CH2:10][CH2:11][O:12][C:13]3[CH:20]=[C:19](Br)[CH:18]=[CH:17][C:14]=32)[CH:8]=1)=[O:6].B1([C:34]2[CH2:39][CH2:38][N:37]([C:40]([O:42][C:43]([CH3:46])([CH3:45])[CH3:44])=[O:41])[CH2:36][CH:35]=2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].C(Cl)Cl>CN(C=O)C>[C:43]([O:42][C:40]([N:37]1[CH2:36][CH:35]=[C:34]([C:19]2[CH:18]=[CH:17][C:14]3[C:15]4[N:9]([CH2:10][CH2:11][O:12][C:13]=3[CH:20]=2)[CH:8]=[C:7]([C:5](=[O:6])[N:4]([CH2:3][CH2:2][OH:1])[CH:22]([CH3:24])[CH3:23])[N:16]=4)[CH2:39][CH2:38]1)=[O:41])([CH3:46])([CH3:44])[CH3:45]

Participants

6

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 58204998HCID 58204998, compound

Product 1

HCID 58204357HCID 58204357, compoundYield 82.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

8-Bromo-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulene-2-carboxylic acid (2-hydroxy-ethyl)-isopropyl-amide (114 mg, 0.28 mmol), 3,6-dihydro-2H-pyridine-1-N-Boc-4-boronic acid pinacol ester (129 mg, 0.62 mmol), potassium carbonate (96 mg, 0.69 mmol) and PdCl2dppf.DCM (20 mg, 0.02 mmol) were suspended in DMF (1.5 mL), and the reaction mixture purged with argon. The reaction mixture was heated at 100° C. for 3 h. The reaction mixture was washed with water, extracted with ethyl acetate (2×15 mL) and the combined organic extracts washed with brine, dried (Na2SO4) and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 0-2% MeOH in DCM) to yield 4-{2-[(2-Hydroxy-ethyl)-isopropyl-carbamoyl]-4,5-dihydro-6-oxa-1,3a-diaza-benzo[e]azulen-8-yl}-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester (115 mg, 80%). LCMS: RT=3.48 min, [M+H]+=497

Workup

  1. customthe reaction mixture purged with argon
  2. washThe reaction mixture was washed with water
  3. extractionextracted with ethyl acetate (2×15 mL)
  4. washthe combined organic extracts washed with brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f1946d0bb49b4ee5b751f50cf94ced3f
Source dataset
uspto-grants-2013_01
Patent number
US08343955B2

Reaction notes

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