Borane;pyridine → HCID 178461422, compound

HRID 2047518Notes

Reaction equation

HRID 2047518 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 2723995Borane;pyridineHCID 6999702(2S)-2-methylpyrrolidineHCID 671459253-(6-Bromobenzothiazol-2-yl)cyclobutanone

Product 1

HCID 178461422HCID 178461422, compoundYield 16%

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-(S)-methylpyrrolidine (1.04 g, 4.43 mmole, toluene extract from 50% sodium hydroxide) was then added and the solution was stirred at room temperature for 30 minutes. Borane-pyridine (358 μl, 3.54 mmole) was added, and the mixture was stirred at room temperature overnight. The reaction was quenched with saturated sodium bicarbonate 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 (0.4% ammonium hydroxide and 4% methanol in dichloromethane) to give 98 mg (16% yield) of the title compound. 1H NMR (500 MHz, CDCl3) δ ppm 7.98 (d, J=2.14 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) 3.00-3.12 (m, 1H) 2.74-2.85 (m, 1H) 2.58-2.68 (m, 1H) 2.43-2.56 (m, 3H) 2.30-2.39 (m, 1H) 1.92-2.02 (m, 1H) 1.78-1.89 (m, 1H) 1.70-1.76 (m, 1H) 1.44-1.59 (m, 1H) 1.16 (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 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 (0.4% ammonium hydroxide and 4% methanol in dichloromethane)

Sources & evidence

ORD record
ord-fd7a35e3a67a4e3b94c02df3ae00a69a
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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