Dichloromethane → Tert-butyl 4-(3-amino-6-(3-oxocyclohex-1-en-1-yl)pyrazin-2-yl)-2-fluorobenzoate

HRID 596119Notes

Reaction equation

HRID 596119 reaction equation
CC1(C)C(C)(C)OB([C:9]2[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[CH:10]=2)O1.[NH2:17][C:18]1[C:19]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[C:27]([F:38])[CH:26]=2)=[N:20][C:21](Br)=[CH:22][N:23]=1.C(Cl)Cl.C([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].CCOCC>[NH2:17][C:18]1[C:19]([C:25]2[CH:37]=[CH:36][C:28]([C:29]([O:31][C:32]([CH3:34])([CH3:35])[CH3:33])=[O:30])=[C:27]([F:38])[CH:26]=2)=[N:20][C:21]([C:9]2[CH2:14][CH2:13][CH2:12][C:11](=[O:15])[CH:10]=2)=[CH:22][N:23]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 574964223-(Tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-en-1-oneHCID 118045500tert-Butyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate

Product 1

HCID 118045378Tert-butyl 4-(3-amino-6-(3-oxocyclohex-1-en-1-yl)pyrazin-2-yl)-2-fluorobenzoateYield 51.3%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 3283Diethyl EtherSolvent

Conditions

Temperature
100 °C

Procedure

A 250 ml RB was charged with 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)cyclohex-2-enone (7.00 g, 31.5 mmol) (in about 70 ml dioxane), tert-butyl 4-(3-amino-6-bromopyrazin-2-yl)-2-fluorobenzoate (5.8 g, 15.75 mmol)), Pd(dppf)Cl2.DCM (0.576 g, 0.788 mmol), and then Saturated Na2CO3 (25 mL). The resultant mixture was flushed with nitrogen for 15 min. DME (10 mL) was then added. The mixture was stirred at 100° C. overnight. Ethyl acetate (150 ml) and water (50 ml) were added, and the resultant mixture was stirred for 30 min. Organics was separated and the aqueous layer was extracted with ethyl acetate (30 ml×3). Organic layers were combined and dried over Na2SO4, filtered and evaporated to provide crude desired material as a sticky dark color semi solid. This solid was taken to about 30 ml of ether, sonicated for 10 min, and the precipitated yellow solid was filtered, and washed with cold ether(5 ml×3), dried under high vacuum to afford the desired product (3.1 g, 51.3%) as a yellow solid. LC-MS (m/z): (MH+) 384.2, 0.92 min.

Workup

  1. customThe resultant mixture was flushed with nitrogen for 15 min
  2. additionDME (10 mL) was then added
  3. additionEthyl acetate (150 ml) and water (50 ml) were added
  4. stirringthe resultant mixture was stirred for 30 min
  5. customOrganics was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (30 ml×3)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customto provide crude desired material as a sticky dark color semi solid
  11. customsonicated for 10 min
  12. filtrationthe precipitated yellow solid was filtered
  13. washwashed with cold ether(5 ml×3)
  14. customdried under high vacuum

Sources & evidence

ORD record
ord-5326cffc14734689a7acbdc8ae08923b
Source dataset
uspto-grants-2016_01
Patent number
US09242996B2

Reaction notes

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