Sodium Carbonate → HCID 71283430, compound

HRID 1752421Notes

Reaction equation

HRID 1752421 reaction equation
[C:1]([C:4]1[CH:9]=[C:8](Cl)[N:7]=[C:6]([NH:11][C@@H:12]([CH3:17])[C:13]([O:15][CH3:16])=[O:14])[N:5]=1)(=[O:3])[NH2:2].[F:18][C:19]1[CH:40]=[CH:39][C:22]([O:23][C:24]2[CH:29]=[CH:28][C:27](B3OC(C)(C)C(C)(C)O3)=[CH:26][CH:25]=2)=[CH:21][CH:20]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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:1]([C:4]1[CH:9]=[C:8]([C:27]2[CH:26]=[CH:25][C:24]([O:23][C:22]3[CH:21]=[CH:20][C:19]([F:18])=[CH:40][CH:39]=3)=[CH:29][CH:28]=2)[N:7]=[C:6]([NH:11][C@@H:12]([CH3:17])[C:13]([O:15][CH3:16])=[O:14])[N:5]=1)(=[O:3])[NH2:2]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 89422566HCID 89422566, compound

Product 1

HCID 71283430HCID 71283430, compoundYield 89.5%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of (S)-methyl 2-((4-carbamoyl-6-chloropyrimidin-2-yl)amino)propanoate (0.642 g, 2.48 mmol) in dioxane (12.5 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.861 g, 2.74 mmol), 2M aqueous Na2CO3 (2.50 mL, 5.00 mmol), and PdCl2(dppf) (0.105 g, 0.129 mmol). The reaction vessel was flushed with argon, sealed, and heated at 80° C. for 5 h. After cooling, the reaction mixture was evaporated in vacuo and the residue chromatographed over silica gel with 20-60% acetone in hexanes. The product fractions were evaporated in vacuo to give (S)-methyl 2-((4-carbamoyl-6-(4-(4-fluorophenoxy)phenyl)pyrimidin-2-yl)amino)propanoate as a tan-yellow glass (0.911 g, 2.22 mmol, 89% yield). LC/MS: m/z=411.2 [M+H]+.

Workup

  1. customThe reaction vessel was flushed with argon
  2. customsealed
  3. temperatureAfter cooling
  4. customthe reaction mixture was evaporated in vacuo
  5. customthe residue chromatographed over silica gel with 20-60% acetone in hexanes
  6. customThe product fractions were evaporated in vacuo

Sources & evidence

ORD record
ord-e64a4205b78643bda13451bf306f23f8
Source dataset
uspto-grants-2015_10
Patent number
US09163008B2

Reaction notes

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