Sodium Carbonate → HCID 58928663, compound

HRID 853690Notes

Reaction equation

HRID 853690 reaction equation
[CH:1]([O:14][C:15]1[C:16]2[C:35](=[O:36])[N:34]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([F:44])=[CH:40][CH:39]=3)[CH2:33][C:17]=2[C:18](OS(C(F)(F)F)(=O)=O)=[C:19]2[C:24]=1[N:23]=[CH:22][CH:21]=[CH:20]2)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH3:51][O:52][C:53]1[C:58](B(O)O)=[CH:57][CH:56]=[CH:55][N:54]=1.CCOC(C)=O.CCCCCC>C1(C)C=CC=CC=1.CCOC(C)=O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:1]([O:14][C:15]1[C:16]2[C:35](=[O:36])[N:34]([CH2:37][C:38]3[CH:39]=[CH:40][C:41]([F:44])=[CH:42][CH:43]=3)[CH2:33][C:17]=2[C:18]([C:58]2[C:53]([O:52][CH3:51])=[N:54][CH:55]=[CH:56][CH:57]=2)=[C:19]2[C:24]=1[N:23]=[CH:22][CH:21]=[CH:20]2)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 21226206Ethyl acetate hexaneHCID 58928818HCID 58928818, compound

Product 1

HCID 58928663HCID 58928663, compound

Reagents, catalysts & solvents 3

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

Alternatively, according to a modified Suzuki coupling method of C. H. Chen; Tetrahedron Letter; EN; 44; 5747-5750; 2003, to a solution of trifluoro-methanesulfonic acid 9-benzhydryloxy-7-(4-fluoro-benzyl)-8-oxo-7,8-dihydro-6H-pyrrolo[3,4-g]quinolin-5-yl ester 46 (266.2 mg, 0.428 mmol) dissolved in toluene (5 mL) was added Na2CO3 (2M in water, 500 μl), 2-methoxypyridine-3-boronic acid (164 mg, 1.07 mmol) and tetrakis-(triphenylphosphine)-palladium(0)(100 mg, 0.086 mmol). The reaction mixture in the flask was flashed with argon three times. It was then heated to 120° C. under argon 4 hours. The reaction was monitored by TLC (EtOAc/hexane 3/7) (Rf1=0.6, Rf17=0.1) and LC/MS. After cooling to room temperature, the mixture was diluted with EtOAc (20 mL) and washed with 1N HCl, saturated NaHCO3 and brine. The organic phase was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel with EtOAc/Hexane (1/1) to afford pure 9-benzhydryloxy-7-(4-fluoro-benzyl)-5-(2-methoxy-pyridin-3-yl)-6,7-dihydro-pyrrolo[3,4-g]quinolin-8-one 288, 125 mg, 50%. 1H NMR (CDCl3) δ 9.0 (dd, 1H), 8.3 (dd, 1H), 8.2 (s, 1H), 7.8 (dd, 4H), 7.7 (dd, 1H), 7.4 (dd, 1H), 7.3-7.1 (m, 8H), 7.0 (m, 2H+1H), 4.7 (dd, 2H), 4.1(dd, 2H), 3.8 (s, 1H); MS: 582 (M+1).

Workup

  1. temperatureAfter cooling to room temperature
  2. washwashed with 1N HCl, saturated NaHCO3 and brine
  3. dry with materialThe organic phase was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography on silica gel with EtOAc/Hexane (1/1)

Sources & evidence

ORD record
ord-e60fcc629e6641ba8612a310d0488d50
Source dataset
uspto-grants-2007_08
Patent number
US07253180B2

Reaction notes

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