N,N'-Dimethylethylenediamine → 6-[6-((R)-3-amino-pyrrolidin-1-yl)-pyridin-3-yl]-2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one

HRID 423427Notes

Reaction equation

[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[NH:13][CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:4][CH:3]=1.Br[C:19]1[CH:20]=[CH:21][C:22]([N:25]2[CH2:29][CH2:28][C@@H:27]([NH:30]C3CC3)[CH2:26]2)=[N:23][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC>O1CCOCC1.[NH4+].[OH-].O.C(Cl)Cl.[Cu]I>[NH2:30][C@@H:27]1[CH2:28][CH2:29][N:25]([C:22]2[N:23]=[CH:24][C:19]([N:13]3[CH:14]=[CH:15][C:10]4[CH:9]=[C:8]([C:5]5[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=5)[S:17][C:11]=4[C:12]3=[O:16])=[CH:20][CH:21]=2)[CH2:26]1

Participants

Conditions

Temperature: 100 °C

Procedure

Degass a mixture of 2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one (374 mg, 1.43 mmol), [(R)-1-(5-bromo-pyridin-2-yl)-pyrrolidin-3-yl]-cyclopropyl-amine (404 mg, 1.43 mmol) and cesium carbonate (932 mg, 2.86 mmol) in 1,4-dioxane (20 mL). Add copper (I) iodide (162 mg, 851 μmol) and sym-dimethylethylene diamine (150 mg, 1.70 mmol). Heat the mixture at 100° C. overnight. Dilute with concentrated NH4OH (5 mL) and water (50 mL) and CH2Cl2. Separate the organics and dry with Na2SO4, filter, and concentrate. Purify using chromatography (0 to 10% MeOH/CH2Cl2) to afford 0.384 g (64%) of 6-[6-((R)-3-amino-pyrrolidin-1-yl)-pyridin-3-yl]-2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one.

Workup

customDegass
customSeparate the organics and
dry with materialdry with Na2SO4
filtrationfilter
concentrationconcentrate
customPurify

Sources & evidence

ORD record: ord-a90a691849144bcca7ea59508b39211f
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08101764B2

Reaction notes

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