Triphenylphosphine → HCID 9805566, compound

HRID 1936353Notes

Reaction equation

HRID 1936353 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.BrN1C(=O)CCC1=O.[Cl:28][C:29]1[CH:30]=[C:31]([CH:41]([CH2:45][CH:46]2[CH2:50][CH2:49][CH2:48][CH2:47]2)[C:42]([OH:44])=O)[CH:32]=[CH:33][C:34]=1[N:35]1[C:39]([CH3:40])=[N:38][N:37]=[N:36]1.[NH2:51][C:52]1[CH:57]=[CH:56][C:55]([Br:58])=[CH:54][N:53]=1>C(Cl)Cl>[Br:58][C:55]1[CH:56]=[CH:57][C:52]([NH:51][C:42](=[O:44])[CH:41]([C:31]2[CH:32]=[CH:33][C:34]([N:35]3[C:39]([CH3:40])=[N:38][N:37]=[N:36]3)=[C:29]([Cl:28])[CH:30]=2)[CH2:45][CH:46]2[CH2:47][CH2:48][CH2:49][CH2:50]2)=[N:53][CH:54]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 67184N-bromobutanimideHCID 706222-Amino-5-bromopyridineHCID 11209847HCID 11209847, compound

Product 1

HCID 9805566HCID 9805566, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (236 mg, 0.9 mmol) in methylene chloride (6 mL) was cooled to 0° C. and then treated with N-bromosuccinimide (160 mg, 0.9 mmol). The reaction mixture was stirred at 0° C. for 30 min and then treated with the 2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-propionic acid (prepared in Example 3, 151 mg, 0.45 mmol). The clear solution was stirred for 15 min at 0° C. and then allowed to warm to 25° C. where it was stirred for 2 h. The reaction mixture was then treated with 2-amino-5-bromopyridine (234 mg, 1.35 mmol), and the resulting suspension was stirred for 2 d at 25° C. The reaction mixture was then concentrated in vacuo to remove methylene chloride, and the residue was diluted with ethyl acetate (30 mL) and water (30 mL). The two layers were separated, and the aqueous layer was extracted with ethyl acetate (1×20 mL). The combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL) and a saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 2/1 hexanes/ethyl acetate) afforded N-(5-bromo-pyridin-2-yl)-2-[3-chloro-4-(5-methyl-tetrazol-1-yl)-phenyl]-3-cyclopentyl-propionamide (90 mg, 42%) as an amorphous white solid: EI-HRMS m/e calcd for C21H22BrClN6O (M+) 489.0727, found 489.0727.

Workup

  1. stirringThe clear solution was stirred for 15 min at 0° C.
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 2 h
  4. stirringthe resulting suspension was stirred for 2 d at 25° C
  5. concentrationThe reaction mixture was then concentrated in vacuo
  6. customto remove methylene chloride
  7. additionthe residue was diluted with ethyl acetate (30 mL) and water (30 mL)
  8. customThe two layers were separated
  9. extractionthe aqueous layer was extracted with ethyl acetate (1×20 mL)
  10. washThe combined organic extracts were successively washed with a saturated aqueous sodium bicarbonate solution (1×50 mL)
  11. dry with materiala saturated aqueous sodium chloride solution (1×50 mL), dried over anhydrous magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-063d17530e7f406fa5f5faf3227066da
Source dataset
uspto-grants-2002_05
Patent number
US06388088B1

Reaction notes

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