Cesium carbonate → HCID 66585037, compound

HRID 589874Notes

Reaction equation

HRID 589874 reaction equation
Br[C:2]1[C:3]([C:21]#[N:22])=[C:4]2[CH2:9][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:7][CH2:6][N:5]2[C:17]=1[CH:18]1[CH2:20][CH2:19]1.[CH3:23][O:24][C:25]1[CH:30]=[CH:29][C:28](B(O)O)=[CH:27][CH:26]=1.C(=O)([O-])[O-:35].[Cs+].[Cs+]>O1CCCC1.O.C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:21]([C:3]1[C:2]([C:28]2[CH:29]=[CH:30][C:25]([O:24][CH3:23])=[CH:26][CH:27]=2)=[C:17]([CH:18]2[CH2:20][CH2:19]2)[N:5]2[CH2:6][CH2:7][N:8]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:9][C:4]=12)(=[O:35])[NH2:22]

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 201262(4-Methoxyphenyl)boronic acidHCID 86680816HCID 86680816, compound

Product 1

HCID 66585037HCID 66585037, compoundYield 47%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of 3.00 g (7.81 mmol) of tert-butyl 7-bromo-8-cyano-6-cyclopropyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylate, 1.54 g (10.2 mmol) of 4-methoxyphenylboronic acid (CAS 5720-07-0) and 7.63 g (23.4 mmol) of caesium carbonate in a mixture of 80 ml of tetrahydrofuran and 4 ml of water under argon is added 0.64 g (0.78 mmol) of 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium (II) (CAS 72287-26-4), and the mixture is heated at 100° C. for 20 hours. After cooling, the mixture is diluted with ethyl acetate and filtered through Celite, 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 40 g of silica gel, eluting with a mixture of 20 to 50% ethyl acetate in dichloromethane, to give 1.51 g of tert-butyl 8-carbamoyl-6-cyclopropyl-7-(4-methoxyphenyl)-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylate in the form of a white solid after crystallizing from a minimum amount of ethyl acetate, rinsing with diethyl ether and drying.

Workup

  1. temperatureAfter cooling
  2. filtrationfiltered through Celite
  3. washthe organic phase is washed with water
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationthe solution is concentrated under reduced pressure
  7. customThe residue is chromatographed on a column of 40 g of silica gel
  8. washeluting with a mixture of 20 to 50% ethyl acetate in dichloromethane

Sources & evidence

ORD record
ord-985ca30b390e4119847a3a00785a9b87
Source dataset
uspto-grants-2016_01
Patent number
US09233965B2

Reaction notes

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