Chloride → HCID 68965552, compound

HRID 2384886Notes

Reaction equation

HRID 2384886 reaction equation
[Cl:1][CH2:2][CH2:3][N:4]1[CH2:8][CH2:7][CH2:6][CH2:5]1.[OH-].[Na+].[CH:11]1([O:14][C:15]2[CH:20]=[CH:19][C:18]([C:21]3[S:39][C:24]4[C:25](=[O:38])[N:26]([C:29]5[CH:34]=[CH:33][C:32]([OH:35])=[C:31]([O:36][CH3:37])[CH:30]=5)[CH2:27][CH2:28][C:23]=4[CH:22]=3)=[CH:17][CH:16]=2)[CH2:13][CH2:12]1.C1(O)C=CC=CC=1.C([O-])([O-])=O.[K+].[K+].[Cl-]>CN(C=O)C.C(Cl)Cl>[ClH:1].[CH:11]1([O:14][C:15]2[CH:16]=[CH:17][C:18]([C:21]3[S:39][C:24]4[C:25](=[O:38])[N:26]([C:29]5[CH:34]=[CH:33][C:32]([O:35][CH2:2][CH2:3][N:4]6[CH2:8][CH2:7][CH2:6][CH2:5]6)=[C:31]([O:36][CH3:37])[CH:30]=5)[CH2:27][CH2:28][C:23]=4[CH:22]=3)=[CH:19][CH:20]=2)[CH2:12][CH2:13]1

Participants

9

Reactant 6

HCID 312ChlorideHCID 996PhenolHCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 816691-(2-Chloroethyl)pyrrolidineHCID 689555942-(4-cyclopropoxy-phenyl)-6-(4-hydroxy-3-methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one

Product 1

HCID 68965552HCID 68965552, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

Make the free base of 2-chloroethylpyrrolidine by adding the hydrochloride salt (84 mg, 0.49 mmol) to a separatory funnel containing 1 N NaOH (75 mL) and CH2Cl2 (75 mL). Wash the organic layer with brine then dry over Na2SO4 and concentrate. In a separate microwave vessel, mix 2-(4-cyclopropoxy-phenyl)-6-(4-hydroxy-3-methoxy-phenyl)-5,6-dihydro-4H-thieno[2,3-c]pyridin-7-one (100 mg, 0.24 mmol) in DMF (1 mL). Warm the mixture slightly with a heat gun until the phenol is in solution. Add powdered K2CO3 (68 mg, 0.49 mmol). Stir 5-10 min at RT and then add the chloride mentioned above as a solution in DMF (500 μL). Cap the vessel and heat under microwave irradiation to 110° C. for 2 h. Load the reaction directly onto a silica gel plug and purify via silica gel chromatography using a 0-10% gradient of (2 N NH3 in MeOH)/CHCl3. Dissolve the freebase of the product in CH2Cl2 (10 mL) and add 1.0 M HCl in Et2O (266 μL). Concentrate to give 48 mg (36%) of the desired product. MS/ES m/z 505.3 [M+H]+.

Workup

  1. washWash the organic layer with brine
  2. dry with materialthen dry over Na2SO4
  3. concentrationconcentrate
  4. customCap the vessel
  5. temperatureheat under microwave irradiation to 110° C. for 2 h
  6. customLoad the reaction directly onto a silica gel plug
  7. custompurify via silica gel chromatography
  8. dissolutionDissolve the freebase of the product in CH2Cl2 (10 mL)
  9. additionadd 1.0 M HCl in Et2O (266 μL)
  10. concentrationConcentrate

Sources & evidence

ORD record
ord-4c4c2b5e6c6a4c6dabe7cf535a84d414
Source dataset
uspto-grants-2012_09
Patent number
US08263772B2

Reaction notes

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