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

HRID 1524127Notes

Reaction equation

HRID 1524127 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[CH:33]=[N:34][C:35]([NH2:38])=[N:36][CH:37]=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].O1CCOCC1.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)=[CH:33][N:34]=1

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 10340Sodium CarbonateHCID 43365405Ethyl 3-(2-bromophenylthio)propanoateHCID 903131425-(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine

Product 1

HCID 90314347Ethyl 3-(4'-(2-aminopyrimidin-5-yl)-5'-fluorobiphenyl-2-ylthio)propanoateYield 82%

Reagents, catalysts & solvents 2

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

Procedure

A mixture of ethyl 3-((2-bromophenyl)thio)propanoate (5.8 g, 20 mmol), 5-(2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)pyrimidin-2-amine (6.95 g, 22.1 mmol), Pd(dppf)Cl2.CH2Cl2 (1.7 g, 2.0 mmol), Na2CO3 (4.25 g, 40.1 mmol) and 1,4-dioxane/water (80 mL/10 mL) was stirred at 90° C. overnight under N2. The reaction mixture was cooled to rt, filtered, and the filtrate concentrated to dryness. The resultant residue was subjected to FCC to give the title compound (6.5 g, 82%). MS (ESI): mass calcd. for C21H20FN3O2S, 397.13; m/z found, 397.9 [M+H]+.

Workup

  1. filtrationfiltered
  2. concentrationthe filtrate concentrated to dryness

Sources & evidence

ORD record
ord-244e3971faab46f1a5f9f3a0c1ef6454
Source dataset
uspto-grants-2015_07
Patent number
US09079866B2

Reaction notes

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