(R)-2-Methylpyrrolidine → HCID 178461420, compound

HRID 2103670Notes

Reaction equation

HRID 2103670 reaction equation
[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([CH:9]3[CH2:12][C:11](=O)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.[CH3:16][C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1.N1C=CC=CC=1.B>ClCCl.C(O)C>[Br:1][C:2]1[CH:15]=[CH:14][C:5]2[N:6]=[C:7]([C@H:9]3[CH2:12][C@@H:11]([N:18]4[CH2:19][CH2:20][CH2:21][C@H:17]4[CH3:16])[CH2:10]3)[S:8][C:4]=2[CH:3]=1

Participants

6

Reactant 3

HCID 641544(R)-2-MethylpyrrolidineHCID 2723995Borane;pyridineHCID 671459253-(6-Bromobenzothiazol-2-yl)cyclobutanone

Product 1

HCID 178461420HCID 178461420, compoundYield 9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent

Procedure

The product of Example 1C (500 mg, 1.77 mmole) was dissolved in 6 ml dichloromethane and 4 ml ethanol. 2-(R)-methylpyrrolidine (1.04 g, 4.43 mmole, toluene extract from 50% sodium hydroxide) was added and stirred at room temperature for 30 minutes. Then borane-pyridine (358 μl, 3.54 mmole) was added. The mixture was stirred at room temperature overnight. The reaction was quenched with saturated sodium bicarbonate and extracted with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure to give the crude product which was purified by column chromatography (0.4% ammonium hydroxide and 4% methanol in dichloromethane) to give 45 mg (9% yield) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 7.98 (d, J=1.83 Hz, 1H) 7.80 (d, J=8.85 Hz, 1H) 7.54 (dd, J=8.54, 1.83 Hz, 1H) 3.54-3.65 (m, 1H) 3.15-3.29 (m, 1H) 3.00-3.13 (m, 1H) 2.73-2.86 (m, 1H) 2.56-2.69 (m, 2H) 2.32-2.57 (m, 3H) 1.92-2.05 (m, 1H) 1.79-1.90 (m, 1H) 1.67-1.78 (m, 1H) 1.46-1.57 (m, 1H) 1.17 (s, 3H). MS: (M+H)+=351/353.

Workup

  1. stirringThe mixture was stirred at room temperature overnight
  2. customThe reaction was quenched with saturated sodium bicarbonate
  3. extractionextracted with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto give the crude product which
  9. customwas purified by column chromatography (0.4% ammonium hydroxide and 4% methanol in dichloromethane)

Sources & evidence

ORD record
ord-1dcd4c3af2094bc4b078cbdc00cead4c
Source dataset
uspto-grants-2009_08
Patent number
US07576110B2

Reaction notes

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