Sodium Carbonate → (S)-4-(3-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide

HRID 595938Notes

Reaction equation

HRID 595938 reaction equation
[NH2:1][C:2]1[C:3]([C:9]2[CH:27]=[CH:26][C:12]([C:13]([NH:15][C@@H:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)[CH2:17][OH:18])=[O:14])=[C:11]([F:28])[CH:10]=2)=[N:4][C:5](Br)=[CH:6][N:7]=1.[CH3:29][N:30]1[CH:34]=[C:33](B2OC(C)(C)C(C)(C)O2)[C:32]([CH3:44])=[N:31]1.C([O-])([O-])=O.[Na+].[Na+].S([O-])([O-])(=O)=O.[Na+].[Na+]>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.COCCOC>[NH2:1][C:2]1[C:3]([C:9]2[CH:27]=[CH:26][C:12]([C:13]([NH:15][C@@H:16]([C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([Cl:25])[CH:20]=3)[CH2:17][OH:18])=[O:14])=[C:11]([F:28])[CH:10]=2)=[N:4][C:5]([C:33]2[C:32]([CH3:44])=[N:31][N:30]([CH3:29])[CH:34]=2)=[CH:6][N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 426473161,3-Dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazoleHCID 118045459HCID 118045459, compound

Product 1

HCID 118045815(S)-4-(3-amino-6-(1,3-dimethyl-1H-pyrazol-4-yl)pyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamideYield 60.4%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To the reaction mixture of (S)-4-(3-amino-6-bromopyrazin-2-yl)-N-(1-(3-chlorophenyl)-2-hydroxyethyl)-2-fluorobenzamide (40 mg, 0.086 mmol), 1,3-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole (38.2 mg, 0.172 mmol), PdCl2(dppf)-DCM (6.28 mg, 8.59 μmol), and DME (644 μL), 2 M Na2CO3 (215 μL) were added. The reaction mixture was heated at microwave synthesizer (120° C., 12 min). To the reaction mixture, anhydrous sodium sulfate was added, filtered, and concentrated. The crude product was purified by auto-prep to provide 25 mg of desired product as a TFA salt. LCMS (m/z): 481.3 (MH+), 0.73 min; 1H NMR (500 MHz, CD3OD) δ ppm 8.66 (d, J=6.26 Hz, 1H) 8.17 (s, 1H) 8.02 (s, 1H) 7.76-7.51 (m, 3H) 7.45-7.16 (m, 3H) 5.07-4.09 (m, 1H) 3.72 (s, 3H) 3.62 (m, 2H) 2.33 (s, 3H).

Workup

  1. additionwere added
  2. filtrationfiltered
  3. concentrationconcentrated
  4. customThe crude product was purified by auto-prep

Sources & evidence

ORD record
ord-a8d83f4ea8fc4afd96c5f353060f3be5
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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