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

HRID 423426Notes

Reaction equation

HRID 423426 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]([N:30]3[CH2:34][CH2:33][C@@H:32]([F:35])[CH2:31]3)[CH2:26]2)=[N:23][CH:24]=1.C(=O)([O-])[O-].[Cs+].[Cs+].CNCCNC.[NH4+].[OH-]>O1CCOCC1.[Cu]I.O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:17][C:11]3[C:12](=[O:16])[N:13]([C:19]4[CH:24]=[N:23][C:22]([N:25]5[CH2:29][CH2:28][C@@H:27]([N:30]6[CH2:34][CH2:33][C@@H:32]([F:35])[CH2:31]6)[CH2:26]5)=[CH:21][CH:20]=4)[CH:14]=[CH:15][C:10]=3[CH:9]=2)=[CH:6][CH:7]=1

Participants

9

Reactant 5

HCID 8070N,N'-DimethylethylenediamineHCID 10796Cesium carbonateHCID 14923Ammonium HydroxideHCID 576495192-(4-Chlorophenyl)-6H,7H-thieno[2,3-c]pyridin-7-oneHCID 66673622(3R,3'R)-1'-(5-Bromo-pyridin-2-yl)-3-fluoro-[1,3']bipyrrolidinyl

Product 1

HCID 666739982-(4-Chloro-phenyl)-6-[6-((3R,3'R)-3-fluoro-[1,3']bipyrrolidinyl-1'-yl)-pyridin-3-yl]-6H-thieno[2,3-c]pyridin-7-oneYield 71%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Degass a mixture of 2-(4-chloro-phenyl)-6H-thieno[2,3-c]pyridin-7-one (458 mg, 1.75 mmol), (3R,3′R)-1′-(5-bromo-pyridin-2-yl)-3-fluoro-[1,3′]bipyrrolidinyl (550 mg, 1.75 mmol) and cesium carbonate (1.14 g, 3.50 mmol) in 1,4-dioxane (20 mL). Add copper (I) iodide (133 mg, 700 μmol) and sym-dimethylethylene diamine (99 μL, 928 μmol). Heat the mixture at 100° C. overnight. Add to the cooled mixture concentrated NH4OH (5 mL). After 10 min, pour the mixture into water (20 mL). Filter the resulting solid and rinse with water (2×), followed by rinsing with Et2O (2×). Purify using chromatography (0 to 5% MeOH/CH2Cl2) to afford 610 mg (71%) of the title compound. 1H NMR (400 MHz, CDCl3) δ: 1.95 (m, 1H), 2.24 (m, 3H), 3.59 (m, 8H), 5.18 (d, 1H), 5.40 (brs, 1H), 6.44 (d, 1H), 6.65 (d, 1H), 7.22 (d, 1H), 7.38 (t, 3H), 7.60 (m, 3H), 8.13 (s, 1H).

Workup

  1. customDegass
  2. filtrationFilter the resulting solid
  3. washrinse with water (2×)
  4. washby rinsing with Et2O (2×)
  5. customPurify

Sources & evidence

ORD record
ord-d56e4df1aac74a3397ec3d3bd09268f6
Source dataset
uspto-grants-2012_01
Patent number
US08101764B2

Reaction notes

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