Cesium carbonate → HCID 86685603, compound

HRID 332810Notes

Reaction equation

HRID 332810 reaction equation
C([N:8]1[CH2:12][CH2:11][C@@H:10]([NH2:13])[CH2:9]1)(OC(C)(C)C)=O.Cl[C:15]1[C:16]([C:22]#[N:23])=[N:17][CH:18]=[C:19](Cl)[N:20]=1.CCN(C(C)C)C(C)C.[NH2:33][C:34]1[CH:35]=[N:36][C:37]2[C:42]([CH:43]=1)=[CH:41][CH:40]=[CH:39][CH:38]=2.C([O-])([O-])=[O:45].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>C(#N)C.C(O)(C(F)(F)F)=O.OS(O)(=O)=O.CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1.O>[NH:8]1[CH2:12][CH2:11][C@@H:10]([NH:13][C:19]2[N:20]=[C:15]([NH:33][C:34]3[CH:35]=[N:36][C:37]4[C:42]([CH:43]=3)=[CH:41][CH:40]=[CH:39][CH:38]=4)[C:16]([C:22]([NH2:23])=[O:45])=[N:17][CH:18]=2)[CH2:9]1

Participants

13

Reactant 6

HCID 10796Cesium carbonateHCID 113753-AminoquinolineHCID 81531DiisopropylethylamineHCID 634876Binap, (A+-)-HCID 854070(R)-(+)-1-Boc-3-aminopyrrolidineHCID 529877443,5-Dichloropyrazine-2-carbonitrile

Product 1

HCID 86685603HCID 86685603, compoundYield 93%

Reagents, catalysts & solvents 6

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 1118Sulfuric AcidSolventHCID 6342AcetonitrileSolventHCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Procedure

Commercially available (R)-(+)-N-Boc-3-aminopyrrolidine (1.0 g, 5.3 mmol) and 3,5-dichloropyrazine-2-carbonitrile (928 mg, 5.1 mmol) were dissolved in ˜25 mL ACN. To this was added 1.4 mL DIEA. The reaction mixture was stirred at room temperature for 30 minutes. Water was added, solid precipitated and was filtered and dried to give crude B58.1 (1.56 g, 93% yield). To 120 mg B58.1 was added 100 mg 3-aminoquinoline (3-AQ), 375 mg Cs2CO3, 60 mg rac-BINAP, and 16 mg Pd(OAc)2. These solids were mixed with 10 mL dioxane and the subsequent suspension was degassed with argon for 5 minutes. The reaction mixture was heated at 100° C. for 3 hours and then cooled down to approximately 60° C. The mixture was filtered and the filtrate was concentrated to give crude B58.2. This crude product was dissolved in 3 mL TFA and 1 mL H2SO4. The mixture was heated at 70° C. for 30 minutes. Volatiles were removed and 5 mL H2O and 1 mL ACN was added to the resulting residue. Precipitate was filtered and the filtrate was subjected to rpHPLC to give the title compound. MS found for C18H19N7O as (M+H)+ 350.2.

Workup

  1. customsolid precipitated
  2. filtrationwas filtered
  3. customdried
  4. customto give crude B58.1 (1.56 g, 93% yield)
  5. customthe subsequent suspension was degassed with argon for 5 minutes
  6. temperatureThe reaction mixture was heated at 100° C. for 3 hours
  7. temperaturecooled down to approximately 60° C
  8. filtrationThe mixture was filtered
  9. concentrationthe filtrate was concentrated
  10. customto give crude B58.2
  11. temperatureThe mixture was heated at 70° C. for 30 minutes
  12. customVolatiles were removed
  13. addition5 mL H2O and 1 mL ACN was added to the resulting residue
  14. filtrationPrecipitate was filtered

Sources & evidence

ORD record
ord-72b56c18270a4a5eb0f7ad675547b557
Source dataset
uspto-grants-2014_11
Patent number
US08877760B2

Reaction notes

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