Sulfuric Acid → HCID 86685627, compound

HRID 2200511Notes

Reaction equation

HRID 2200511 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15]C(=O)[O-])[CH:5]=[N:4][C:3]=1[C:19]#[N:20].[NH2:21][C:22]1[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=1.C(=O)([O-])[O-:29].[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.OS(O)(=O)=O>O1CCOCC1.C(O)(C(F)(F)F)=O.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:6]1[N:7]=[C:2]([NH:21][C:22]2[CH:23]=[N:24][CH:25]=[CH:26][CH:27]=2)[C:3]([C:19]([NH2:20])=[O:29])=[N:4][CH:5]=1

Participants

10

Reactant 5

HCID 1118Sulfuric AcidHCID 100093-AminopyridineHCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 86685625((1S,2R)-2-((6-chloro-5-cyanopyrazin-2-yl)amino)cyclohexyl)carbamate

Product 1

HCID 86685627HCID 86685627, compoundYield 112.4%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6422Trifluoroacetic acidSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

The mixture of tert-tutyl ((1S,2R)-2-((6-chloro-5-cyanopyrazin-2-yl)amino)cyclohexyl)carbamate (100 mg, 0.28 mmol), 3-aminopyridine (53 mg, 0.56 mmol), powder cesium carbonate (360 mg, 1.12 mmol), BINAP (37 mg, 0.06 mmol), Pd(OAc)2 (14 mg, 0.06 mmol) in 20 mL dioxane was degassed with argon stream. It was stirred in argon atmosphere at 110° C. for 2 h. The mixture was cooled, diluted with 100 mL EtOAc, vigorously stirred, and filtered through celite. The filtrate was concentrated and subjected to silica flash column with 0-70% EtOAc in hexane to isolate the coupling product. It was then stirred in 6 mL TFA and 1 mL conc. H2SO4 at 80° C. for 30 m. It was cooled in ice bath, diluted with water, filtered, and subjected to reverse phase preparative HPLC to isolate the title compound (103 mg). MS found for C16H21N7O as (M+H)+328.5. UV: λ=230, 259, 301 nm. 1H NMR: (CD3OD) δ 9.50 (1H, s), 8.56 (1H, d, J=8.8 Hz), 8.42 (1H, d, J=5.6 Hz), 7.95 (1H, dd, J=8.8; 5.6 Hz), 7.75 (1H, s), 4.57 (1H, m), 3.70 (1H, m), 1.95-1.58 (8H, m) ppm.

Workup

  1. customwas degassed with argon stream
  2. temperatureThe mixture was cooled
  3. additiondiluted with 100 mL EtOAc
  4. stirringvigorously stirred
  5. filtrationfiltered through celite
  6. concentrationThe filtrate was concentrated
  7. customto isolate the coupling product
  8. customat 80° C.
  9. temperatureIt was cooled in ice bath
  10. filtrationfiltered

Sources & evidence

ORD record
ord-838e60f24aca4b5580e026862c4c8a6a
Source dataset
uspto-grants-2016_06
Patent number
US09359308B2

Reaction notes

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