Sodium Carbonate → HCID 58513533, compound

HRID 1405056Notes

Reaction equation

HRID 1405056 reaction equation
Cl[C:2]1[C:7]([C:8]#[C:9][C:10]2[CH:11]=[N:12][C:13]([NH2:16])=[CH:14][CH:15]=2)=[C:6]([CH3:17])[N:5]=[C:4]([NH2:18])[N:3]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH:30]=[C:29](B2OC(C)(C)C(C)(C)O2)[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C([O-])([O-])=O.[Na+].[Na+].[Li+].[Cl-]>C1(C)C=CC=CC=1.C(O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:19]([O:23][C:24]([N:26]1[CH2:27][CH:28]=[C:29]([C:2]2[C:7]([C:8]#[C:9][C:10]3[CH:11]=[N:12][C:13]([NH2:16])=[CH:14][CH:15]=3)=[C:6]([CH3:17])[N:5]=[C:4]([NH2:18])[N:3]=2)[CH2:30][CH2:31]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 433294Lithium ChlorideHCID 4642098Tert-butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,6-tetrahydropyridine-1-carboxylateHCID 58513427HCID 58513427, compound

Product 1

HCID 58513533HCID 58513533, compoundYield 82.1%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21863594Toluene ethanolSolvent

Procedure

A mixture of 500 mg (1.9 mmol) 4-chloro-6-methyl-5-(6-amino-pyridin-3-ylethynyl)-pyrimidin-2-ylamine, 1.2 g (3.9 mmol) 4-(4,4,5,5-tetramethyl-[1,3,2]-dioxaborolan-2-yl)-3,6-dihydro-2H-pyridine-1-carboxylic acid tert-butyl ester, 135 mg (1.9 mmol) Pd(PPh3)2Cl2, 40 mL 1 M aqueous Na2CO3 solution and 244 mg LiCl (5.78 mmol) in 100 mL toluene/ethanol (4:1 v/v) is kept over 2 days at reflux. After cooling the solvent is evaporated, water is added and the aqueous suspension is extracted 4 times with ethyl acetate (200 mL each). The organic layer is dried over MgSO4 and the solvent is removed under reduced pressure. The residue is purified using flash column chromatography yielding 635 mg (1.56 mmol) of the desired product which is used without further purification in the next step.

Workup

  1. temperatureat reflux
  2. temperatureAfter cooling the solvent
  3. customis evaporated
  4. additionwater is added
  5. extractionthe aqueous suspension is extracted 4 times with ethyl acetate (200 mL each)
  6. dry with materialThe organic layer is dried over MgSO4
  7. customthe solvent is removed under reduced pressure
  8. customThe residue is purified

Sources & evidence

ORD record
ord-abd8b09b3df24fc09b3e1e31fe4fbb82
Source dataset
uspto-grants-2014_12
Patent number
US08916548B2

Reaction notes

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