Sodium Carbonate → HCID 57980113, compound

HRID 1867857Notes

Reaction equation

HRID 1867857 reaction equation
Br[C:2]1[CH:7]=[C:6]([F:8])[C:5]([C:9]([N:11]2[CH2:15][CH2:14][CH2:13][C@H:12]2[CH2:16][N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:10])=[C:4]([F:22])[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[N:29]1[CH:34]=[CH:33][CH:32]=[C:31](B(O)O)[CH:30]=1>C1(C)C=CC=CC=1.O.C(O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:8][C:6]1[CH:7]=[C:2]([C:31]2[CH:30]=[N:29][CH:34]=[CH:33][CH:32]=2)[CH:3]=[C:4]([F:22])[C:5]=1[C:9]([N:11]1[CH2:15][CH2:14][CH2:13][C@H:12]1[CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1)=[O:10]

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 11965202HCID 11965202, compound

Product 1

HCID 57980113HCID 57980113, compoundYield 2.2%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

Procedure WW: To a stirred solution of (4-Bromo-2,6-difluoro-phenyl)-((S)-2-pyrrolidin-1-ylmethyl-pyrrolidin-1-yl)-methanone (100 mg, 0.268 mmol), sodium carbonate (85 mg, 0.802 mmol) and 3-pyridine boronic acid (164 mg, 1.34 mmol) in toluene (5 ml), water (1 ml) and ethanol (1.5 ml) under nitrogen is added Tetrakis (triphenylphosphine) palladium (0) (31.0 mg, 0.027 mmol). The reaction is heated at reflux for 48 h. The reaction is allowed to cool and bound to a SCX-2 cartridge (10 g). The cartridge is washed with one cartridge volume of dimethylformamide and two volumes of methanol. The product is eluted using 2M ammonia in methanol. The ammonia/methanol solution is evaporated on a Genevac HT4. The sample is further purified by prep-LCMS. The resulting acetonitrile/water fractions are combined and evaporated using a Genevac to give 2.2 mg of a colourless oil (2%). MS (ES+) 372.2 m/z

Workup

  1. temperatureThe reaction is heated
  2. temperatureat reflux for 48 h
  3. temperatureto cool
  4. washThe cartridge is washed with one cartridge volume of dimethylformamide and two volumes of methanol
  5. washThe product is eluted
  6. customThe ammonia/methanol solution is evaporated on a Genevac HT4
  7. customThe sample is further purified by prep-LCMS
  8. customevaporated

Sources & evidence

ORD record
ord-141101a50bce46f1b96fb0aa0292986b
Source dataset
uspto-grants-2009_12
Patent number
US07632857B2

Reaction notes

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