Ethyl Acetate → HCID 118046105, compound

HRID 595944Notes

Reaction equation

HRID 595944 reaction equation
[NH2:1][C:2]1[N:3]=[CH:4][C:5](B(O)O)=[N:6][C:7]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14](=[O:25])[NH:15][C@@H:16]([C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH2:17][OH:18])=[CH:10][CH:9]=1.Br[C:30]1[CH:31]=[CH:32][C:33](=[O:36])[NH:34][CH:35]=1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>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].C(Cl)Cl>[NH2:1][C:2]1[C:7]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([NH:15][C@@H:16]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:17][OH:18])=[O:25])=[CH:10][CH:9]=2)=[N:6][C:5]([C:30]2[CH:31]=[CH:32][C:33](=[O:36])[NH:34][CH:35]=2)=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 5995285-Bromo-2-hydroxypyridineHCID 131734606HCID 131734606, compound

Product 1

HCID 118046105HCID 118046105, compoundYield 6.9%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of (S)-5-amino-6-(4-(2-hydroxy-1-phenylethylcarbamoyl)phenyl)pyrazin-2-ylboronic acid (55 mg, 0.145 mmol), 5-bromopyridin-2(1H)-one (38.0 mg, 0.218 mmol), and PdCl2(dppf)-CH2Cl2 (11.88 mg, 0.015 mmol) in DME (1091 μL) was added 2M Na2CO3 (364 μL). The reaction mixture was heated at microwave synthesizer (120° C., 10 min). The reaction mixture was worked up 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 by prep HPLC yielding 4.3 mg of (S)-4-(3-amino-6-(6-oxo-1,6-dihydropyridin-3-yl)pyrazin-2-yl)-N-(2-hydroxy-1-phenylethyl)benzamide as a TFA salt. LCMS (m/z): 428.2 (MH+), 0.55 min; 1H NMR (400 MHz, DMSO-d6) 3.60-3.75 (m, 2H) 5.03-5.12 (m, 1H) 6.40 (d, J=9.39 Hz, 1H) 7.22 (d, J=7.43 Hz, 1H) 7.30 (t, J=7.63 Hz, 2H) 7.34-7.40 (m, 2H) 7.83 (d, J=8.22 Hz, 2H) 7.94 (br. s., 1H) 8.01 (d, J=8.61 Hz, 2H) 8.06 (dd, J=9.39, 2.74 Hz, 1H) 8.41 (s, 1H) 8.74 (d, J=8.22 Hz, 1H).

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 by prep HPLC

Sources & evidence

ORD record
ord-6e3b488216fd45ca8dc3925ed00e57ed
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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