Sodium Carbonate → HCID 54597166, compound

HRID 2174662Notes

Reaction equation

HRID 2174662 reaction equation
[CH2:1]([O:8][C:9]1[C:10]([NH2:16])=[N:11][CH:12]=[C:13](Br)[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])([O-])=O.[Na+].[Na+].[CH:23]([N:26]1[CH:31]=[C:30](B2OC(C)(C)C(C)(C)O2)[CH:29]=[CH:28][C:27]1=[O:41])([CH3:25])[CH3:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CCC=1>C(#N)C.Cl[Pd]Cl.[Fe].ClCCl>[NH2:16][C:10]1[N:11]=[CH:12][C:13]([C:30]2[CH:29]=[CH:28][C:27](=[O:41])[N:26]([CH:23]([CH3:25])[CH3:24])[CH:31]=2)=[N:14][C:9]=1[O:8][CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 3524393Cyclopenta-1,4-dien-1-yl(diphenyl)phosphaneHCID 107551623-(Benzyloxy)-5-bromopyrazin-2-amineHCID 580703861-Isopropyl-6-oxo-1,6-dihydropyridine-3-boronic Acid Pinacol Ester

Product 1

HCID 54597166HCID 54597166, compoundYield 13.3%

Reagents, catalysts & solvents 4

HCID 23925IronCatalystHCID 24290Palladium ChlorideCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

3-(benzyloxy)-5-bromopyrazin-2-amine (100 mg, 0.358 mmol) was dissolved in acetonitrile (4 mL). Aqueous Na2CO3 solution (462.3 μL of 2 M, 0.9247 mmol), 1-isopropyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridin-2-one (146.0 mg, 0.5548 mmol) and cyclopenta-1,4-dien-1-yl(diphenyl)phosphane; dichloromethane; dichloropalladium; iron (75.33 mg, 0.09247 mmol) was added and the reaction mixture was heated for 30 minutes at 100° C. under microwave conditions. The reaction mixture was concentrated in vacuo and the residue was partitioned between DCM and water. The layers were separated and the aqueous further extracted with DCM. The combined organic extract was dried (MgSO4), filtered and concentrated in vacuo. This material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected, and freeze-dried to give the title compound (16 mg, 6.13% Yield). H1 NMR (400.0 MHz, DMSO) δ 1.35 (d, J=6.8 Hz, 6H), 5.10 (m, J=6.8 Hz, 1H), 5.53 (s, 2H), 6.46 (d, J=9.5 Hz, 1H), 7.32 (m, J=7.3 Hz, 1H), 7.38-7.41 (m, 2H), 7.54 (d, J=7.2 Hz, 2H), 7.95 (dd, J=2.5, 9.5 Hz, 1H), 7.98 (s, 1H) and 8.06 (d, J=2.5 Hz, 1H). MS (ES+) 337.0

Workup

  1. concentrationThe reaction mixture was concentrated in vacuo
  2. customthe residue was partitioned between DCM and water
  3. customThe layers were separated
  4. extractionthe aqueous further extracted with DCM
  5. extractionThe combined organic extract
  6. dry with materialwas dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThis material was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 μM, 100 Å column, gradient 10%-95% B (solvent A: 0.05% TFA in water; solvent B: CH3CN) over 16 minutes at 25 mL/min]
  10. customThe fractions were collected
  11. customfreeze-dried

Sources & evidence

ORD record
ord-b03129a4b43e4e9d97392930e316c033
Source dataset
uspto-grants-2015_06
Patent number
US09062008B2

Reaction notes

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