Pyrrolidine → HCID 178419316, compound

HRID 2047525Notes

Reaction equation

HRID 2047525 reaction equation
[NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.[Br:6][C:7]1[CH:20]=[CH:19][C:10]2[N:11]=[C:12]([CH:14]3[CH2:17][C:16](=O)[CH2:15]3)[S:13][C:9]=2[CH:8]=1.C([BH3-])#N.[Na+]>CO>[Br:6][C:7]1[CH:20]=[CH:19][C:10]2[N:11]=[C:12]([C@H:14]3[CH2:15][C@@H:16]([N:1]4[CH2:5][CH2:4][CH2:3][CH2:2]4)[CH2:17]3)[S:13][C:9]=2[CH:8]=1

Participants

5

Reactant 3

HCID 31268PyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 671459253-(6-Bromobenzothiazol-2-yl)cyclobutanone

Product 1

HCID 178419316HCID 178419316, compoundYield 55%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Pyrrolidine (295 μl, 3.54 mmol) was added to a solution of the product of Example 1C (100 mg, 0.354 mmole) in 2 ml methanol and the mixture was stirred at room temperature for 1 hour. Sodium cyanoborohydride (56 mg, 0.891 mmole) was added and the resulting mixture was stirred at room temperature overnight. The reaction was quenched with water and extracted three times with dichloromethane. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to give the crude product which was purified by column chromatography (0.5% ammonium hydroxide and 5% methanol in dichloromethane) to give 65 mg (55%) of the title compound. 1H NMR (400 MHz, CDCl3) for the cis isomer δ ppm 7.97 (d, J=1.84 Hz, 1H) 7.80 (d, J=8.90 Hz, 1H) 7.54 (dd, J=8.75, 1.99 Hz, 1H) 3.56-3.66 (m, 1H) 3.05-3.19 (m, 1H) 2.55-2.75 (m, 6H) 2.41-2.53 (m, 2H) 1.75-1.92 (m, 4H). MS: (M+H)+=337/339.

Workup

  1. stirringthe resulting mixture was stirred at room temperature overnight
  2. customThe reaction was quenched with water
  3. extractionextracted three times with dichloromethane
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product which
  9. customwas purified by column chromatography (0.5% ammonium hydroxide and 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-9eae419fbca747c283fd21d92bc94d98
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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