Cesium carbonate → tert-butyl 3-(4-((4-((3S)-3-cyano-3-isopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylate

HRID 714881Notes

Reaction equation

HRID 714881 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]2[CH2:12][CH2:11][C@:10]([CH:15]([CH3:17])[CH3:16])([C:13]#[N:14])[C:9]2=[O:18])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[CH:21]=[N:22][N:23]([CH:25]2[CH2:28][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:26]2)[CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(O)(C)(C)C.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]>[C:13]([C@@:10]1([CH:15]([CH3:17])[CH3:16])[CH2:11][CH2:12][N:8]([C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]3[CH:21]=[N:22][N:23]([CH:25]4[CH2:28][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:26]4)[CH:24]=3)[N:7]=2)[C:9]1=[O:18])#[N:14]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 272815264-Amino-1-(1-Boc-azetidin-3-yl)-1H-pyrazoleHCID 117840068(3S)-1-(2-chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile

Product 1

HCID 117840309tert-butyl 3-(4-((4-((3S)-3-cyano-3-isopropyl-2-oxopyrrolidin-1-yl)pyrimidin-2-yl)amino)-1H-pyrazol-1-yl)azetidine-1-carboxylateYield 11.6%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 6386tert-ButanolSolvent

Conditions

Temperature
100 °C

Procedure

To a mixture of (3S)-1-(2-chloropyrimidin-4-yl)-3-isopropyl-2-oxopyrrolidine-3-carbonitrile (200 mg) obtained in Step A of Example 9, tert-butyl 3-(4-amino-1H-pyrazol-1-yl)azetidine-1-carboxylate (97 mg) obtained in Step B of Example 131, cesium carbonate (370 mg) and dicyclohexyl(2′,4′,6′-triisopopropyl-3,6-dimethoxybiphenyl-2-yl)phosphine (57 mg) in tert-butanol (2.0 mL) was added tris(dibenzylideneacetone)dipalladium(0) (48 mg), and the mixture was stirred at 100° C. for 5 hr. 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 (hexane/ethyl acetate) to give the title compound (22 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 (hexane/ethyl acetate)

Sources & evidence

ORD record
ord-b39590378f0c47b383f91f325e86f1b6
Source dataset
uspto-grants-2015_11
Patent number
US09187453B2

Reaction notes

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