Dichloromethane → (S)-4-(3-amino-6-bromopyrazin-2-yl)-N-(2-hydroxy-1-phenylethyl)benzamide

HRID 595943Notes

Reaction equation

HRID 595943 reaction equation
Br[C:2]1[C:3]([NH2:9])=[N:4][CH:5]=[C:6]([Br:8])[N:7]=1.[OH:10][CH2:11][C@@H:12]([NH:19][C:20](=[O:36])[C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.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].CCOC(C)=O>[NH2:9][C:3]1[C:2]([C:24]2[CH:25]=[CH:26][C:21]([C:20]([NH:19][C@@H:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[CH2:11][OH:10])=[O:36])=[CH:22][CH:23]=2)=[N:7][C:6]([Br:8])=[CH:5][N:4]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 6200042-Amino-3,5-dibromopyrazineHCID 123160895(S)-N-(2-hydroxy-1-phenylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide

Product 1

HCID 118046143(S)-4-(3-amino-6-bromopyrazin-2-yl)-N-(2-hydroxy-1-phenylethyl)benzamideYield 118.5%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3,5-dibromopyrazin-2-amine (826 mg, 3.27 mmol), (S)—N-(2-hydroxy-1-phenylethyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (600 mg, 1.634 mmol), and PdCl2(dppf).CH2Cl2 adduct (133 mg, 0.163 mmol) in DME (12.3 mL) was added 2 M Na2CO3 (4.08 mL). The reaction mixture was heated at microwave synthesizer (120° C., 10 min). The reaction mixture was worked uup with EtOAc. The organic layer was washed with sat NaHCO3, water and brine, dried over Na2SO4, filtered off, concentrated in vacuo. The crude product was purified with silica flash chromatography eluting with 0-100% of EtOAc (containing 10% of MeOH) in heptane, and triturated with ether to provide 800 mg of (S)-4-(3-amino-6-bromopyrazin-2-yl)-N-(2-hydroxy-1-phenylethyl)benzamide. LCMS (m/z): 415 (MH+), 0.73 min.

Workup

  1. washThe organic layer was washed with sat NaHCO3, water and brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered off
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified with silica flash chromatography
  6. washeluting with 0-100% of EtOAc (containing 10% of MeOH) in heptane
  7. customtriturated with ether

Sources & evidence

ORD record
ord-80534c2d80bf4f4c82388fd5cf0df5c2
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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