Sodium Carbonate → Methyl 4-(3-amino-6-(4-((benzyloxy)methyl)cyclohex-1-en-1-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596115Notes

Reaction equation

HRID 596115 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.[CH2:20]([O:27][CH2:28][CH:29]1[CH2:34][CH2:33][C:32](B2OC(C)(C)C(C)(C)O2)=[CH:31][CH2:30]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC>[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:32]2[CH2:33][CH2:34][CH:29]([CH2:28][O:27][CH2:20][C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH2:30][CH:31]=2)=[CH:6][N:7]=1

Participants

5

Reactant 3

HCID 10340Sodium CarbonateHCID 118046172Methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoateHCID 1317346262-(4-((Benzyloxy)methyl)cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 118046409Methyl 4-(3-amino-6-(4-((benzyloxy)methyl)cyclohex-1-en-1-yl)pyrazin-2-yl)-2-fluorobenzoateYield 81%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
115 °C

Procedure

Methyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (343 mg, 1.051 mmol), 2-(4-((benzyloxy)methyl)cyclohex-1-en-1-yl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (414 mg, 1.261 mmol) PdCl2(dppf)-CH2Cl2 adduct (86 mg, 0.105 mmol) were placed in a microwave vial and then DME (3.5 mL) was added. Then 2.0 M Na2CO3 (1261 μL, 2.52 mmol) was added and the mixture was degassed and purged with nitrogen and then heated at 115° C. for 30 min upon which the reaction was complete. The reaction mixture was diluted with EtOAc and washed with water and the organic layer was separated and dried (MgSO4), filtered and concentrated and the residue purified by flash chromatography (0-100% EtOAc/heptane) to afford 381 mg the desired product as a yellow solid (81%). LCMS (m/z): 448.2 (MH+), 1.16 min.

Workup

  1. customthe mixture was degassed
  2. custompurged with nitrogen
  3. additionThe reaction mixture was diluted with EtOAc
  4. washwashed with water
  5. customthe organic layer was separated
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customthe residue purified by flash chromatography (0-100% EtOAc/heptane)

Sources & evidence

ORD record
ord-14c48958325b4f31b7f8ace3e449e872
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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