Sodium Carbonate → methyl 4-(3-amino-6-(1H-pyrazol-4-yl) pyrazin-2-yl)-2-fluorobenzoate

HRID 596097Notes

Reaction equation

HRID 596097 reaction equation
[NH2:1][C:2]1[C:3]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([F:19])[CH:10]=2)=[N:4][C:5](Br)=[CH:6][N:7]=1.C(=O)([O-])[O-].[Na+].[Na+].CC1(C)C(C)(C)OB([C:34]2[CH:35]=[N:36][N:37](C(OC(C)(C)C)=O)[CH:38]=2)O1>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:3]([C:9]2[CH:18]=[CH:17][C:12]([C:13]([O:15][CH3:16])=[O:14])=[C:11]([F:19])[CH:10]=2)=[N:4][C:5]([C:34]2[CH:35]=[N:36][NH:37][CH:38]=2)=[CH:6][N:7]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 16217654tert-butyl 4-(tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylateHCID 118046172Methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045485methyl 4-(3-amino-6-(1H-pyrazol-4-yl) pyrazin-2-yl)-2-fluorobenzoate

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
120 °C

Procedure

To methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (For Synthesis see Example 34, Step 2) (100 mg, 0.307 mmol) in DME (3 mL) and 2 M sodium carbonate (0.75 mL, 1.5 mmol) was added tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (90 mg, 0.307 mmol) followed by PdCl2(dppf)-CH2Cl2 adduct (25.04 mg, 0.031 mmol). The reaction mixture was heated in microwave at 120° C. for 15 min. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered and evaporated. The residue was proceeded to next step without purification (90 mg, 74%, 80% purity). LCMS (m/z): 314.1 (MH+), 0.595 min.

Workup

  1. customThe reaction mixture was partitioned between ethyl acetate and water
  2. customThe organic layer was separated
  3. washwashed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customThe residue was proceeded to next step without purification (90 mg, 74%, 80% purity)
  8. custom314.1 (MH+), 0.595 min.

Sources & evidence

ORD record
ord-51c3bcfce5fe4065abc7f11dfb919562
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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