Cesium carbonate → HCID 54761459, compound

HRID 589877Notes

Reaction equation

HRID 589877 reaction equation
[C:1]([NH:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:21]3[CH2:23][CH2:22]3)=[C:15](Br)[C:16]([C:17]([NH2:19])=[O:18])=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:24][O:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.C(O)C>[C:1]([NH:5][C:6]([N:8]1[CH2:13][CH2:12][N:11]2[C:14]([CH:21]3[CH2:23][CH2:22]3)=[C:15]([C:29]3[CH:30]=[CH:31][C:26]([O:25][CH3:24])=[CH:27][CH:28]=3)[C:16]([C:17]([NH2:19])=[O:18])=[C:10]2[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 66584858HCID 66584858, compound

Product 1

HCID 54761459HCID 54761459, compoundYield 23.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture under nitrogen of 0.750 g (1.96 mmol) of N2-tert-butyl-7-bromo-6-cyclopropyl-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide, 0.446 g (2.94 mmol) of 4-methoxyphenylboronic acid (CAS 5720-07-0) and 5.8 ml (12 mmol) of aqueous 2M caesium carbonate solution in a mixture of 15 ml of toluene and 15 ml of ethanol under argon is added 0.64 g (0.78 mmol) of tetrakis(triphenyl-phosphine)palladium (CAS 14221-01-3), and the mixture is heated at 100° C. for 17 hours. After cooling, the mixture is filtered through Celite and the filtrate concentrated under reduced pressure. The residue is then taken up in dichloromethane, the organic phase is washed with water, dried over sodium sulfate and filtered, and the solution is concentrated under reduced pressure. The residue is chromatographed on a column of 15 g of silica gel, eluting with a mixture of 10 to 100% ethyl acetate in dichloromethane, to give 0.19 g of N2-tert-butyl-6-cyclo-propyl-7-(4-methoxyphenyl)-3,4-dihydropyrrolo[1,2-a]pyrazine-2,8(1H)-dicarboxamide in the form of a white solid after crystallizing from a minimum amount of ethyl acetate, rinsing with diethyl ether and drying, and is identical to the compound obtained according to the procedure of Example 12.

Workup

  1. temperatureAfter cooling
  2. filtrationthe mixture is filtered through Celite
  3. concentrationthe filtrate concentrated under reduced pressure
  4. washthe organic phase is washed with water
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationthe solution is concentrated under reduced pressure
  8. customThe residue is chromatographed on a column of 15 g of silica gel
  9. washeluting with a mixture of 10 to 100% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-9ce0e6d7f77a492bab5a637f52a0e687
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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