Potassium Carbonate → HCID 178461421, compound

HRID 2047509Notes

Reaction equation

HRID 2047509 reaction equation
[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](O)[CH2:10]3)[S:8][C:4]=2[CH:3]=1.C(=O)([O-])[O-].[K+].[K+].FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([C@@H]([C@H](C(O)=O)O)O)(O)=O.[CH3:47][C@@H:48]1[CH2:52][CH2:51][CH2:50][NH:49]1>ClCCl>[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:49]4[CH2:50][CH2:51][CH2:52][C@H:48]4[CH3:47])[CH2:10]3)[S:8][C:4]=2[CH:3]=1

Participants

6

Reactant 4

HCID 11430Potassium Carbonate2×HCID 67749Trifluoromethanesulfonic anhydrideHCID 11858493(R)-2-methylpyrrolidine L-tartrateHCID 178521623HCID 178521623, compound

Product 1

HCID 178461421HCID 178461421, compoundYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The product of Example 1D (2.52 mmole) was dissolved in anhydrous dichloromethane (20 ml). Potassium carbonate (696 mg, 5.04 mmole) was added followed by trifluoromethanesulfonic anhydride (551 μl, 3.27 mmole). The mixture was allowed to stir at room temperature for 2 hours, then another portion of potassium carbonate (1.74 g, 12.6 mmole) was added, followed by 2-(R)-methylpyrrolidine L-tartrate (prepared according to the procedure that described in: R. Altenbach et al., WO 2004043458, and Y. Pu et al., Organic Process Research & Development, 9(1), 45-50, 2005) (1.18 g, 5.04 mmole). The resulting mixture was stirred at room temperature overnight. It was then quenched with water, and extracted three times with dichloromethane. The organic layers were combined, washed with brine, dried over sodium sulfate, and concentrated. The crude product was purified by column chromatography (0.5% ammonium hydroxide and 5% methanol in dichloromethane) to give 394 mg (45%) of title compound. 1H NMR (400 MHz, CDCl3) δ ppm 7.97 (d, J=1.84 Hz, 1H), 7.83 (d, J=8.90 Hz, 1H), 7.55 (dd, J=8.75, 1.99 Hz, 1H), 3.75-3.88 (m, 1H), 3.40-3.56 (m, 1H), 3.00-3.10 (m, 1H), 2.61-2.79 (m, 3H), 2.42-2.57 (m, 2H), 2.23-2.37 (m, 1H), 1.88-2.02 (m, 1H), 1.77-1.88 (m, 1H), 1.61-1.76 (m, 1H), 1.39-1.54 (m, 1H), 1.11 (d, J=6.14 Hz, 3H). MS: (M+H)+=351/353.

Workup

  1. customprepared
  2. stirringThe resulting mixture was stirred at room temperature overnight
  3. customIt was then quenched with water
  4. extractionextracted three times with dichloromethane
  5. washwashed with brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe crude product was purified by column chromatography (0.5% ammonium hydroxide and 5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-789708b05e424b01bc5a3a1e567f1f55
Source dataset
uspto-grants-2013_11
Patent number
US08592467B2

Reaction notes

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