Cesium carbonate → Ethyl 6-chloro-7-(4-(6-phenylpyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylate

HRID 1626443Notes

Reaction equation

HRID 1626443 reaction equation
[C:1]([C:4]1[CH:26]=[CH:25][C:7]([O:8][C:9]2[CH:18]=[C:17]3[C:12]([CH:13]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[CH2:14][CH2:15][O:16]3)=[CH:11][C:10]=2[Cl:24])=[CH:6][CH:5]=1)(=[O:3])[NH2:2].Cl[C:28]1[CH:33]=[N:32][CH:31]=[C:30]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[N:29]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCCC1>[Cl:24][C:10]1[CH:11]=[C:12]2[C:17](=[CH:18][C:9]=1[O:8][C:7]1[CH:6]=[CH:5][C:4]([C:1](=[O:3])[NH:2][C:28]3[CH:33]=[N:32][CH:31]=[C:30]([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[N:29]=3)=[CH:26][CH:25]=1)[O:16][CH2:15][CH2:14][CH:13]2[C:19]([O:21][CH2:22][CH3:23])=[O:20]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 52160922-Chloro-6-phenylpyrazineHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 67288619Ethyl 7-(4-carbamoylphenoxy)-6-chlorochroman-4-carboxylate

Product 1

HCID 67289163Ethyl 6-chloro-7-(4-(6-phenylpyrazin-2-ylcarbamoyl)phenoxy)chroman-4-carboxylateYield 92.2%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

Argon was bubbled through a tetrahydrofuran (665 μl) solution of ethyl 7-(4-carbamoylphenoxy)-6-chlorochroman-4-carboxylate (50 mg, 0.133 mmol; Example 45, step A) and 2-chloro-6-phenylpyrazine (25.4 mg, 0.133 mmol) at ambient temperature in a vial. Cesium carbonate (47.7 mg, 0.146 mmol), XPHOS ligand (12.7 mg, 0.0266 mmol), and tris(dibenzylideneacetone)dipalladium (0) (6.09 mg, 0.0066 mmol) were added. Argon was bubbled through the reaction for two minutes and the vial was capped. The reaction was heated to 60° C. (oil bath temperature) for 18 hours. The reaction was cooled to ambient temperature and applied to silica gel. Elution with a gradient of ethyl acetate/hexanes (20 to 85%) provided the title compound (65 mg, 92%) as an off-white solid.

Workup

  1. customArgon was bubbled through the reaction for two minutes
  2. customthe vial was capped
  3. temperatureThe reaction was cooled to ambient temperature
  4. washElution with a gradient of ethyl acetate/hexanes (20 to 85%)

Sources & evidence

ORD record
ord-b089c6e34de04948847d96fb534e2c4c
Source dataset
uspto-grants-2014_07
Patent number
US08785445B2

Reaction notes

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