Cesium carbonate → (3r)-(3-Methoxy-pyrrolidin-1-yl)-[7-(2-methyl-1h-indol-5-yloxy)-thieno[3,2-b]pyridin-2-yl]-methanone

HRID 889882Notes

Reaction equation

HRID 889882 reaction equation
C([O-])([O-])=O.[Cs+].[Cs+].Cl[C:8]1[CH:13]=[CH:12][N:11]=[C:10]2[CH:14]=[C:15]([C:17]([N:19]3[CH2:23][CH2:22][C@@H:21]([O:24][CH3:25])[CH2:20]3)=[O:18])[S:16][C:9]=12.[CH3:26][C:27]1[NH:28][C:29]2[C:34]([CH:35]=1)=[CH:33][C:32]([OH:36])=[CH:31][CH:30]=2>CN(C=O)C>[CH3:25][O:24][C@@H:21]1[CH2:22][CH2:23][N:19]([C:17]([C:15]2[S:16][C:9]3[C:10](=[N:11][CH:12]=[CH:13][C:8]=3[O:36][C:32]3[CH:33]=[C:34]4[C:29](=[CH:30][CH:31]=3)[NH:28][C:27]([CH3:26])=[CH:35]4)[CH:14]=2)=[O:18])[CH2:20]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 833362-methyl-1H-indol-5-olHCID 207677657-chloro-2-[(R)-3-methoxypyrrolidine-1-carbonyl]thieno[3,2-b]pyridine

Product 1

HCID 10223104(3r)-(3-Methoxy-pyrrolidin-1-yl)-[7-(2-methyl-1h-indol-5-yloxy)-thieno[3,2-b]pyridin-2-yl]-methanoneYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Cs2CO3 (0.495 g, 1.52 mmol) was added to a solution of (3R)-(7-chloro-thieno[3,2-b]pyridin-2-yl)-(3-methoxy-pyrrolidin-1-yl)-methanone (0.228 g, 0.76 mmol) and 2-methyl-1H-indol-5-ol (0.223 9, 1.52 mmol) in DMF (5 mL), and the resulting solution was heated to 90° C. After 20 h the reaction was quenched with water, EtOAc was added, and the layers were separated. The aqueous layer was extracted with EtOAc, and the combined organic layers were dried over Na2SO4 then concentrated. The resulting material was purified on silica gel by flash column chromatography, eluting with CH2Cl2/MeOH (98/2) to afford the title compound as a white solid (0.26 g, 84%). MS: 408.8 (MH+); HPLC Rf: 5.394 min.; HPLC purity: 97%.

Workup

  1. customAfter 20 h the reaction was quenched with water, EtOAc
  2. additionwas added
  3. customthe layers were separated
  4. extractionThe aqueous layer was extracted with EtOAc
  5. dry with materialthe combined organic layers were dried over Na2SO4
  6. concentrationthen concentrated
  7. customThe resulting material was purified on silica gel by flash column chromatography
  8. washeluting with CH2Cl2/MeOH (98/2)

Sources & evidence

ORD record
ord-be1de9888ff34679a55b4e1e6369b7ef
Source dataset
uspto-grants-2006_02
Patent number
US06995171B2

Reaction notes

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