Sodium Carbonate → {1-[4-(6-Oxo-8-phenyl-1,6-dihydro-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-7-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester

HRID 1037387Notes

Reaction equation

HRID 1037387 reaction equation
I[C:2]1[C:3](=[O:21])[C:4]2[C:9]([O:10][C:11]=1[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)=[C:8]1[NH:18][N:19]=[CH:20][C:7]1=[CH:6][CH:5]=2.[C:22]([O:26][C:27](=[O:48])[NH:28][C:29]1([C:33]2[CH:38]=[CH:37][C:36](B3OC(C)(C)C(C)(C)O3)=[CH:35][CH:34]=2)[CH2:32][CH2:31][CH2:30]1)([CH3:25])([CH3:24])[CH3:23].C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.COCCOC>[C:22]([O:26][C:27](=[O:48])[NH:28][C:29]1([C:33]2[CH:38]=[CH:37][C:36]([C:2]3[C:3](=[O:21])[C:4]4[C:9]([O:10][C:11]=3[C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[C:8]3[NH:18][N:19]=[CH:20][C:7]3=[CH:6][CH:5]=4)=[CH:35][CH:34]=2)[CH2:30][CH2:31][CH2:32]1)([CH3:24])([CH3:25])[CH3:23]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 58326444tert-Butyl (1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)cyclobutyl)carbamate2×HCID 670677727-Iodo-8-phenyl-1H-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-6-one

Product 1

HCID 67067899{1-[4-(6-Oxo-8-phenyl-1,6-dihydro-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-7-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl esterYield 42.2%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
125 °C

Procedure

To a microwave vial were added 7-iodo-8-phenyl-1H-9-oxa-1,2-diaza-cyclopenta[a]naphthalen-6-one (100 mg, 0.257 mmol), {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (115 mg, 0.308 mmol), sodium carbonate solution (2 M in water, 1 mL), tetrakis(triphenylphosphine)palladium(0) (44.5 mg, 0.039 mmol) and DME (3 mL). The reaction mixture was purged using nitrogen and heated in a microwave reactor at 125° C. for 1 hour. Further portions of {1-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-cyclobutyl}-carbamic acid tert-butyl ester (50 mg, 0.134 mmol) and tetrakis(triphenylphosphine)palladium(0) (20 mg, 0.017 mmol) were added and the mixture was heated in a microwave reactor at 125° C. for a further 1 hour. The reaction mixture was partitioned between EtOAc and water and the resulting biphasic mixture was separated. The aqueous phase was extracted with EtOAc and the combined organic phase was washed with water and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The resultant residue was subjected to flash chromatography (SiO2, gradient 30 to 70% EtOAc in cyclohexane) to afford the title compound (55.1 mg, 42%) as a yellow gum. LCMS (Method H): RT=3.95 min, [M+H]+=508.

Workup

  1. customThe reaction mixture was purged
  2. temperaturethe mixture was heated in a microwave reactor at 125° C. for a further 1 hour
  3. customThe reaction mixture was partitioned between EtOAc and water
  4. customthe resulting biphasic mixture was separated
  5. extractionThe aqueous phase was extracted with EtOAc
  6. washthe combined organic phase was washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb6654fbd6c74b609eaa9b7975ec45e3
Source dataset
uspto-grants-2013_10
Patent number
US08546376B2

Reaction notes

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