Cesium carbonate → 2-(5-((4-((3R)-3-cyano-3-ethyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)pyridin-2-yl)acetamide hydrochloride

HRID 714914Notes

Reaction equation

HRID 714914 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH2:15][CH3:16])([C:13]#[N:14])[C:9]2=[O:17])[CH:5]=[CH:4][N:3]=1.[NH2:18][C:19]1[CH:20]=[CH:21][C:22]([CH2:25][C:26]([NH2:28])=[O:27])=[N:23][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[ClH:1].[C:13]([C@@:10]1([CH2:15][CH3:16])[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:18][C:19]3[CH:20]=[CH:21][C:22]([CH2:25][C:26]([NH2:28])=[O:27])=[N:23][CH:24]=3)[N:7]=2)[C:9]1=[O:17])#[N:14]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 687181332-(5-Aminopyridin-2-yl)acetamideHCID 117840665(3R)-1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 1178398852-(5-((4-((3R)-3-cyano-3-ethyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)pyridin-2-yl)acetamide hydrochlorideYield 20.3%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (3R)-1-(2-chloropyrimidin-4-yl)-3-ethyl-2-oxopyrrolidine-3-carbonitrile (130 mg) obtained in Step A of Example 8, 2-(5-aminopyridin-2-yl)acetamide (78 mg) obtained in Step D of Example 363, cesium carbonate (340 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (48 mg) in tetrahydrofuran (5.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (48 mg), and the mixture was stirred overnight at 80° C. under argon atmosphere. The insoluble substance was removed by filtration through Celite, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (NH, ethyl acetate/methanol). To a solution of the residue (200 mg) in ethanol (2.0 mL) was added 1 M hydrochloric acid (0.55 mL), the mixture was stirred at room temperature for 5 min, and the solvent was evaporated under reduced pressure. The obtained crude crystals were recrystallized (diisopropyl ether/ethanol) to give the title compound (42 mg).

Workup

  1. customThe insoluble substance was removed by filtration through Celite
  2. customthe solvent was evaporated under reduced pressure
  3. customThe residue was purified by silica gel column chromatography (NH, ethyl acetate/methanol)
  4. additionTo a solution of the residue (200 mg) in ethanol (2.0 mL) was added 1 M hydrochloric acid (0.55 mL)
  5. stirringthe mixture was stirred at room temperature for 5 min
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained crude crystals
  8. customwere recrystallized (diisopropyl ether/ethanol)

Sources & evidence

ORD record
ord-827b1a51ad7e4eceb2f3e4711a2abf02
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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