Sodium Carbonate → 3-[2-(2-Fluoro-phenyl)-4-pyrrolo[3,2-c]pyridin-1-yl-quinazolin-6-yl]-benzamide

HRID 2387260Notes

Reaction equation

HRID 2387260 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[F:18])[N:6]=[C:5]2[N:19]1[C:27]2[CH:26]=[CH:25][N:24]=[CH:23][C:22]=2[CH:21]=[CH:20]1.C(=O)([O-])[O-].[Na+].[Na+].B(O)(O)[C:35]1[CH:40]=[CH:39][CH:38]=[C:37]([C:41]([NH2:43])=[O:42])[CH:36]=1>O1CCCC1.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>[F:18][C:13]1[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=1[C:7]1[N:6]=[C:5]([N:19]2[C:27]3[CH:26]=[CH:25][N:24]=[CH:23][C:22]=3[CH:21]=[CH:20]2)[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:35]3[CH:36]=[C:37]([CH:38]=[CH:39][CH:40]=3)[C:41]([NH2:43])=[O:42])[CH:3]=2)[N:8]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2737814(3-Carbamoylphenyl)boronic acidHCID 103647546-Bromo-2-(2-fluoro-phenyl)-4-pyrrolo[3,2-c]pyridin-1-yl-quinazoline

Product 1

HCID 184406453-[2-(2-Fluoro-phenyl)-4-pyrrolo[3,2-c]pyridin-1-yl-quinazolin-6-yl]-benzamideYield 26.5%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

6-Bromo-2-(2-fluoro-phenyl)-4-pyrrolo[3,2-c]pyridin-1-yl-quinazoline from Step E, Example 3 (0.1 g, 0.23 mmol) was dissolved in tetrahydrofuran (5 ml). Sodium carbonate (0.075 g, 0.7 mmol) and benzamide-3-boronic acid (0.040 g, 0.24 mmol) was added followed by tetrakis(triphenylphosphine)palladium(0) (0.005 g, 0.004 mmol) after degassing for 5 mins. Water (0.5 ml) was added drop wise and the mixture was magnetically stirred and heated to 80° C. for 4 hrs. Water was added and product extracted with ethyl acetate. The ethyl acetate layer was dried and evaporated in a rotary evaporator and the residue further purified using a HPLC reverse phase column using an acetonitrile and water gradient containing 0.1% trifluoroacetic acid to yield the title compound (0.028 g, 25%). MS (ES) 460.0 (M+H)+

Workup

  1. customafter degassing for 5 mins
  2. additionWater (0.5 ml) was added drop wise
  3. additionWater was added
  4. extractionproduct extracted with ethyl acetate
  5. dry with materialThe ethyl acetate layer was dried
  6. customevaporated in a rotary evaporator
  7. customthe residue further purified
  8. additioncontaining 0.1% trifluoroacetic acid

Sources & evidence

ORD record
ord-3c53dc7ca21e4ecd915644a4f1bf646a
Source dataset
uspto-grants-2012_09
Patent number
US08268857B2

Reaction notes

Loading…