Water → (2S)-(2-Methoxymethyl-pyrrolidin-1-yl)-[7-(2-methyl-quinolin-6ylamino)-thieno[3,2-b]pyridin-2-yl]-methanone

HRID 1063233Notes

Reaction equation

HRID 1063233 reaction equation
[C:1](=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][CH2:21][CH:20]3[CH2:24][OH:25])=[O:18])[S:16][C:9]=12.[CH3:26][C:27]1[CH:36]=[CH:35][C:34]2[C:29](=[CH:30][CH:31]=[C:32]([NH2:37])[CH:33]=2)[N:28]=1.O>CN(C=O)C>[CH3:1][O:25][CH2:24][C@@H:20]1[CH2:21][CH2:22][CH2:23][N:19]1[C:17]([C:15]1[S:16][C:9]2[C:10](=[N:11][CH:12]=[CH:13][C:8]=2[NH:37][C:32]2[CH:33]=[C:34]3[C:29](=[CH:30][CH:31]=2)[N:28]=[C:27]([CH3:26])[CH:36]=[CH:35]3)[CH:14]=1)=[O:18]

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 1031482-Methylquinolin-6-amineHCID 22143523(7-Chloro-thieno[3,2-b]pyridin-2-yl)-(2-hydroxymethyl-pyrrolidin-1-yl)-methanone

Product 1

HCID 23401149(2S)-(2-Methoxymethyl-pyrrolidin-1-yl)-[7-(2-methyl-quinolin-6ylamino)-thieno[3,2-b]pyridin-2-yl]-methanone

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

Cesium Carbonate (117 mg, 0.36 mmol) was added to a solution of (7-chloro-thieno[3,2-b]pyridin-2-yl)-(2-hydroxymethyl-pyrrolidin-1-yl)-methanone 1(56 mg, 0.18 mmol) in DMF (4 mL). The reaction mixture was heated to 85° C. for 1.5 hours with stirring. After cooling to room temperature, 2-methyl-quinolin-6-ylamine (57 mg, 0.36 mmol) was added to the reaction mixture, and the resulting mixture was heated to 90° C. for 48 hours. The reaction mixture was treated with water and extracted with EtOAc (3×15 mL). The combined organic extracts were was dried over sodium sulfate, and the solvent was removed under reduced pressure. Purification by flash chromatography on silica gel with CH2Cl2/MeOH (95/5) afforded the title compound as a white solid. MS: 435 (MH+); HPLC Rf: 5.35 min; HPLC purity: 97%.

Workup

  1. temperatureAfter cooling to room temperature
  2. temperaturethe resulting mixture was heated to 90° C. for 48 hours
  3. extractionextracted with EtOAc (3×15 mL)
  4. dry with materialThe combined organic extracts were was dried over sodium sulfate
  5. customthe solvent was removed under reduced pressure
  6. customPurification by flash chromatography on silica gel with CH2Cl2/MeOH (95/5)

Sources & evidence

ORD record
ord-4454c6118dd84821a27fdce970ce0588
Source dataset
uspto-grants-2005_11
Patent number
US06964961B2

Reaction notes

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