Sodium Carbonate → HCID 67994842, compound

HRID 2361425Notes

Reaction equation

HRID 2361425 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(C3C=CC=CC=3)(C3C=CC=CC=3)C3C=CC=CC=3)[CH2:15][CH2:14][C:5]=1[NH:6]2.CC1C(B2OC(C)(C)C(C)(C)O2)=CC=CC=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.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>[CH3:4][C:3]1[C:7]([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:8][CH:9]=[CH:10][C:2]=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][NH:16][CH2:15][CH2:14][C:5]=1[NH:6]2

Participants

7

Reactant 3

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

Product 1

HCID 67994842HCID 67994842, compoundYield 114.9%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Alternatively, a mixture of 9-bromo-2-trityl-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole-6-carboxamide (78.3 mg, 0.146 mmol), 3-(2-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)quinazolin-4(3H)-one (52.9 mg, 0.146 mmol), and 2 M aqueous sodium carbonate (0.219 mL, 0.438 mmol) in toluene (1.2 mL) and ethanol (0.3 mL) was degassed by bubbling with argon for ca. 5-10 min (1 minute with sonication). The mixture was treated with tetrakis(triphenylphosphine)palladium (8.4 mg, 0.007 mmol) and heated at 90° C. under argon. After 15.75 h, the mixture was cooled to room temperature and concentrated under vacuum. The residue was stirred in methanol, treated with a small amount of TFA and water and the resulting mixture was sonicated until the gummy insoluble material was replaced by a flocculent precipitate. The mixture was filtered and subjected to purification by preparative HPLC. Fractions containing the desired product by LCMS were combined, treated with saturated aqueous sodium bicarbonate and concentrated under vacuum to provide an aqueous suspension. The precipitate was collected by filtration, washed with water and dried under vacuum to provide the desired product as a white solid (37.7 mg, 56% yield). LCMS (M+H+) m/z 450.2. 1H NMR (400 MHz, DMSO-d6) δ 10.83-10.93 (1 H, m), 8.19-8.41 (2 H, m), 8.03 (1 H, br. s.), 7.86-7.97 (1 H, m), 7.79 (1 H, t, J=7.3 Hz), 7.58-7.70 (2 H, m), 7.41-7.57 (2 H, m), 7.23-7.41 (2 H, m), 6.74-6.88 (1 H, m), 3.02-3.28 (2 H, m), 2.90 (2 H, br. s.), 2.71 (2 H, br. s.), 1.76 (3 H, s).

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. concentrationconcentrated under vacuum
  6. additiontreated with a small amount of TFA and water
  7. customthe resulting mixture was sonicated until the gummy insoluble material
  8. filtrationThe mixture was filtered
  9. customsubjected to purification by preparative HPLC
  10. additionFractions containing the desired product by LCMS
  11. additiontreated with saturated aqueous sodium bicarbonate
  12. concentrationconcentrated under vacuum
  13. customto provide an aqueous suspension
  14. filtrationThe precipitate was collected by filtration
  15. washwashed with water
  16. customdried under vacuum

Sources & evidence

ORD record
ord-2e8126ee7ef14edd894feb53979238c7
Source dataset
uspto-grants-2014_04
Patent number
US08685969B2

Reaction notes

Loading…