(3S)-(-)-3-(Dimethylamino)pyrrolidine → (S)-1-(4-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)benzyl)-N,N-dimethylpyrrolidin-3-amine

HRID 418612Notes

Reaction equation

HRID 418612 reaction equation
Cl[CH2:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:17][C:16]3[C:11](=[N:12][CH:13]=[CH:14][C:15]=3[O:18][C:19]3[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:20]=3[F:28])[CH:10]=2)=[CH:5][CH:4]=1.[CH3:29][N:30]([CH3:36])[C@H:31]1[CH2:35][CH2:34][NH:33][CH2:32]1>COCCOC>[F:28][C:20]1[CH:21]=[C:22]([N+:25]([O-:27])=[O:26])[CH:23]=[CH:24][C:19]=1[O:18][C:15]1[CH:14]=[CH:13][N:12]=[C:11]2[CH:10]=[C:9]([C:6]3[CH:5]=[CH:4][C:3]([CH2:2][N:33]4[CH2:34][CH2:35][C@H:31]([N:30]([CH3:36])[CH3:29])[CH2:32]4)=[CH:8][CH:7]=3)[S:17][C:16]=12

Participants

4

Reactant 2

HCID 7019156(3S)-(-)-3-(Dimethylamino)pyrrolidineHCID 594245202-(4-(Chloromethyl)phenyl)-7-(2-fluoro-4-nitrophenoxy)thieno[3,2-b]pyridine

Product 1

HCID 58790373(S)-1-(4-(7-(2-Fluoro-4-nitrophenoxy)thieno[3,2-b]pyridin-2-yl)benzyl)-N,N-dimethylpyrrolidin-3-amineYield 38%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a suspension of 52 (1.0 g, 2.41 mmol) in DME (˜20 ml) was added (S)—N,N-dimethylpyrrolidin-3-amine (413 mg, 3.62 mmol) and TEA (486 mg, 2 eq, 4.82 mmol) and the reaction mixture was heated to reflux for an hour. The reaction mixture was cooled to RT, filtered then concentrated. The mixture was partitioned between EtOAc/H2O and the biphasic system was filtered and the resultant yellow solid was collected was collected by filtration to afford title compound 60 (450 mg, 38% yield). The organic phase was separated from the biphasic system; it was then dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (9:1 EtOAc:MeOH+1% conc NH4OH solution) to afford an additional amount of 60 (82 mg, 7% yield). MS (m/z): 493 (M+H).

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureto reflux for an hour
  3. filtrationfiltered
  4. concentrationthen concentrated
  5. customThe mixture was partitioned between EtOAc/H2O
  6. filtrationthe biphasic system was filtered
  7. customthe resultant yellow solid was collected
  8. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-07edbc7294e94f7fae6ef9f6ee1ded67
Source dataset
uspto-grants-2012_01
Patent number
US08093264B2

Reaction notes

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