Chloroform → (R)-(3-(Dimethylamino)pyrrolidin-1-yl)(7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)methanone

HRID 418585

Reaction equation

HRID 418585 reaction equation
Cl[C:2]1[CH:7]=[CH:6][N:5]=[C:4]2[CH:8]=[C:9]([C:11]([N:13]3[CH2:17][CH2:16][C@@H:15]([N:18]([CH3:20])[CH3:19])[CH2:14]3)=[O:12])[S:10][C:3]=12.[F:21][C:22]1[CH:27]=[C:26]([N+:28]([O-:30])=[O:29])[CH:25]=[CH:24][C:23]=1[OH:31].C([O-])([O-])=O.[K+].[K+].C(Cl)(Cl)Cl>O(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:19][N:18]([CH3:20])[C@@H:15]1[CH2:16][CH2:17][N:13]([C:11]([C:9]2[S:10][C:3]3[C:4](=[N:5][CH:6]=[CH:7][C:2]=3[O:31][C:23]3[CH:24]=[CH:25][C:26]([N+:28]([O-:30])=[O:29])=[CH:27][C:22]=3[F:21])[CH:8]=2)=[O:12])[CH2:14]1

Participants

6

Reactant 4

HCID 6212ChloroformHCID 98252-Fluoro-4-nitrophenolHCID 11430Potassium CarbonateHCID 20745989(R)-(7-Chlorothieno[3,2-b]pyridin-2-yl)(3-(dimethylamino)pyrrolidin-1-yl)methanone

Product 1

HCID 58790264(R)-(3-(Dimethylamino)pyrrolidin-1-yl)(7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)methanoneYield 71%

Reagents, catalysts & solvents 1

HCID 7583Diphenyl EtherSolvent

Conditions

Temperature
190 °C

Procedure

A mixture of the amide 24 (1.44 g, 4.65 mmol), 2-fluoro-4-nitrophenol (2.21 g, 14.1 mmol) and K2CO3 (2.56 g, 18.5 mmol) in Ph2O (5.0 mL) was heated at 190° C. for 3 hrs. CHCl3 (100 mL) was added to the resultant dark brown mixture and then the mixture was extracted with 1M HCl. The aqueous phase was washed with CHCl3 and basified with NH4OH (pH 11). The resultant cloudy mixture was extracted with CHCl3 and the organic phase was collected, washed with water, dried over anhydrous Na2SO4 then concentrated under reduced pressure. The remaining yellow solid material was purified by flash chromatography, eluent CHCl3/MeOH (95:5, then 80:20) to afford title compound 25 as a white solid (1.41 g, 3.28 mmol, 71% yield). MS (m/z): 431.0 (M+H).

Workup

  1. extractionthe mixture was extracted with 1M HCl
  2. washThe aqueous phase was washed with CHCl3
  3. extractionThe resultant cloudy mixture was extracted with CHCl3
  4. customthe organic phase was collected
  5. washwashed with water
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationthen concentrated under reduced pressure
  8. customThe remaining yellow solid material was purified by flash chromatography, eluent CHCl3/MeOH (95:5

Sources & evidence

ORD record
ord-4655200704354f03a128a854ccfb2396
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Linked notes

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