Sodium Carbonate → HCID 67994678, compound

HRID 2361423Notes

Reaction equation

HRID 2361423 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:8]([C:11]([NH2:13])=[O:12])=[C:7]2[C:3]=1[C:4]1[CH2:17][N:16]([C:18]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:15][CH2:14][C:5]=1[NH:6]2.[CH3:37][C:38]1[C:43](B2OC(C)(C)C(C)(C)O2)=[CH:42][CH:41]=[CH:40][C:39]=1[N:53]1[C:62](=[O:63])[C:61]2[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=2)[N:55]=[CH:54]1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C(O)C.CCOC(C)=O.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>[CH3:37][C:38]1[C:39]([N:53]2[C:62](=[O:63])[C:61]3[C:56](=[CH:57][CH:58]=[CH:59][CH:60]=3)[N:55]=[CH:54]2)=[CH:40][CH:41]=[CH:42][C:43]=1[C:2]1[CH:10]=[CH:9][C:8]([C:11]([NH2:13])=[O:12])=[C:7]2[C:3]=1[C:4]1[CH2:17][N:16]([C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH2:15][CH2:14][C:5]=1[NH:6]2

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 67994603HCID 67994603, compoundHCID 67994896HCID 67994896, compound

Product 1

HCID 67994678HCID 67994678, compoundYield 75.4%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 9-bromo-2-trityl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-6-carboxamide (250 mg, 0.466 mmol), 3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)quinazolin-4(3H)-one (186 mg, 0.513 mmol), and 2 M aqueous sodium carbonate (0.699 mL, 1.398 mmol) in toluene (4 mL) and ethanol (1 mL) was degassed by bubbling with argon for ca. 5-10 min (1 minute with sonication). The mixture was treated with tetrakis(triphenylphosphine)palladium (26.9 mg, 0.023 mmol) and heated at 90° C. under argon. After 16 h, the mixture was cooled to room temperature, diluted with EtOAc and a small amount of water and the layers were separated. The aqueous phase was extracted with EtOAc and the combined organic phases were filtered, dried and concentrated. The residue was subjected to column chromatography on silica gel (40 g), eluting with EtOAc-hexane (gradient from 15:85 to 100:0) to provide the desired product as a light yellow glass (243 mg, 70% yield). LCMS (M+H-trityl)+ m/z 450.2.

Workup

  1. customwas degassed
  2. customby bubbling with argon for ca. 5-10 min
  3. custom(1 minute with sonication)
  4. temperaturethe mixture was cooled to room temperature
  5. customa small amount of water and the layers were separated
  6. extractionThe aqueous phase was extracted with EtOAc
  7. filtrationthe combined organic phases were filtered
  8. customdried
  9. concentrationconcentrated
  10. washeluting with EtOAc-hexane (gradient from 15:85 to 100:0)

Sources & evidence

ORD record
ord-aba4209118dd41fa8029533931afcee7
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

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