Dichloromethane → Ethyl 3-(4'-(5-aminopyrazin-2-yl)-5'-fluorobiphenyl-2-ylthio)propanoate

HRID 1523843Notes

Reaction equation

HRID 1523843 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8][CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[F:16][C:17]1[CH:22]=[C:21](B2OC(C)(C)C(C)(C)O2)[CH:20]=[CH:19][C:18]=1[C:32]1[N:33]=[CH:34][C:35]([NH2:38])=[N:36][CH:37]=1.C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.O.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].O>[NH2:38][C:35]1[N:36]=[CH:37][C:32]([C:18]2[C:17]([F:16])=[CH:22][C:21]([C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=3[S:8][CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:20][CH:19]=2)=[N:33][CH:34]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 43365405Ethyl 3-(2-bromophenylthio)propanoateHCID 903122765-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-phenyl)-pyrazin-2-amine

Product 1

HCID 90313441Ethyl 3-(4'-(5-aminopyrazin-2-yl)-5'-fluorobiphenyl-2-ylthio)propanoateYield 80.7%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

A mixture of ethyl 3-(2-bromophenylthio)propanoate (7 g, 24 mmol), 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrazin-2-amine (7.6 g, 24 mmol), Pd(dppf)Cl2.CH2Cl2 (378 mg, 0.52 mmol) and Na2CO3 (5 g, 48 mmol) in dioxane/water (20 mL/5 mL) was stirred at 80° Celsius for 5 hours under N2, then poured into water (60 mL) and extracted with EtOAc (50 mL×3). The combined organic extracts were dried over Na2SO4, filtered, concentrated to dryness and purified by FCC to give ethyl 3-(4′-(5-aminopyrazin-2-yl)-5′-fluorobiphenyl-2-ylthio)propanoate (7.7 g, 80%) as a white solid. MS (ESI): mass calcd. for C21H20FN3O2S, 397.13; m/z found, 397.9 [M+H]+.

Workup

  1. extractionextracted with EtOAc (50 mL×3)
  2. dry with materialThe combined organic extracts were dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. custompurified by FCC

Sources & evidence

ORD record
ord-8f3283a2af954806a35f1ffdf63c88e6
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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