Sodium Carbonate → HCID 59331639, compound

HRID 1255849Notes

Reaction equation

HRID 1255849 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[CH:12]=[C:13]([NH:17][C:18](=[O:29])[C:19]3[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=3)[CH:14]=[CH:15][CH:16]=2)[CH3:10])[CH:5]=[N:4][CH:3]=1.[OH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+].[Cl-].[Na+].O.O>CN(C)C=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]>[OH:30][CH2:31][C:32]1[CH:37]=[CH:36][C:35]([C:2]2[N:7]=[C:6]([NH:8][C@H:9]([C:11]3[CH:12]=[C:13]([NH:17][C:18](=[O:29])[C:19]4[CH:24]=[CH:23][CH:22]=[C:21]([C:25]([F:28])([F:27])[F:26])[CH:20]=4)[CH:14]=[CH:15][CH:16]=3)[CH3:10])[CH:5]=[N:4][CH:3]=2)=[CH:34][CH:33]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 23713072Sodium chloride dihydrateHCID 25218456HCID 25218456, compound

Product 1

HCID 59331639HCID 59331639, compoundYield 33%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a degassed solution of (S)—N-(3-(1-(6-chloropyrazin-2-ylamino)ethyl)phenyl)-3-(trifluoromethyl)benzamide (210 mg, 0.5 mmol), 4-(hydroxymethyl)phenylboronic acid (152 mg, 1 mmol) and aqueous sodium carbonate (0.62 mL, 2M, 1.55 mmol) in N,N-dimethyl formamide (3 mL) was added dichloro[1,1′-bis(diphenylphosphino)ferrocene)palladium(II) (24 mg, 0.03 mmol) and the mixture was heated at 80° C. for 18 hours in a sealed tube. After this time the mixture was allowed to cool, was poured into a mixture of brine/water (2:3, 50 mL) and was extracted with a mixture of ethyl acetate/tetrahydrofuran (4:1, 3×30 mL). The combined organic extracts were concentrated under reduced pressure and the residue was taken up in ethyl acetate (50 mL), dried (Na2SO4) and concentrated under reduced pressure to give a black oil which was purified by flash chromatography (silica, ethyl acetate/hexanes) to give (S)—N-(3-(1-(6-(4-(hydroxymethyl)phenyl)pyrazin-2-ylamino)ethyl)phenyl)-3-(trifluoromethyl)benzamide (80 mg, 33%) as a pale yellow solid.

Workup

  1. temperatureto cool
  2. extractionwas extracted with a mixture of ethyl acetate/tetrahydrofuran (4:1, 3×30 mL)
  3. concentrationThe combined organic extracts were concentrated under reduced pressure
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give a black oil which
  7. customwas purified by flash chromatography (silica, ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fbb8b3eb62404469800e3a8b641f0df7
Source dataset
uspto-grants-2013_06
Patent number
US08461161B2

Reaction notes

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