Triphenylphosphine → HCID 10337781, compound

HRID 1816166Notes

Reaction equation

HRID 1816166 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:37]=[C:36]2[C:32]([C:33]([C:41]([OH:43])=O)=[CH:34][N:35]2[CH:38]([CH3:40])[CH3:39])=[CH:31][CH:30]=1.[NH2:44][C:45]1[CH:50]=[CH:49][C:48]([Cl:51])=[CH:47][N:46]=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.C(OCC)(=O)C>[Cl:51][C:48]1[CH:49]=[CH:50][C:45]([NH:44][C:41]([C:33]2[C:32]3[C:36](=[CH:37][C:29]([Cl:28])=[CH:30][CH:31]=3)[N:35]([CH:38]([CH3:39])[CH3:40])[CH:34]=2)=[O:43])=[N:46][CH:47]=1

Participants

9

Reactant 5

HCID 11776TriphenylphosphineHCID 661742-Amino-5-chloropyridineHCID 67184N-bromobutanimideHCID 516892Sodium BicarbonateHCID 224972296-Chloro-1-(propan-2-yl)-1H-indole-3-carboxylic acid

Product 1

HCID 10337781HCID 10337781, compoundYield 29%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of triphenylphosphine (243 mg, 0.92 mmol) in methylene chloride (3 mL) cooled to 0° C. was treated with N-bromosuccinimide (165 mg, 0.92 mmol). This solution was stirred at 0° C. for 15 min. At this time, the reaction was treated with 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid (200 mg, 0.84 mmol). This solution was stirred at 0° C. for 15 min and then was allowed to warm to 25° C. where it was stirred for 30 min. The reaction was then treated with 2-amino-5-chloropyridine (270 mg, 2.10 mmol) and was then stirred at 25° C. for 40 h. At this time, the reaction was diluted with water (25 mL) and ethyl acetate (25 mL). This mixture was treated with a saturated aqueous sodium bicarbonate solution (10 mL). The organic layer was separated and was washed with a saturated aqueous sodium chloride solution (1×25 mL), dried over magnesium sulfate, filtered, and concentrated in vacuo. Biotage chromatography (FLASH 40S, Silica, 5/1 hexanes/ethyl acetate) afforded 6-chloro-1-isopropyl-1H-indole-3-carboxylic acid (5-chloro-pyridin-2-yl)-amide (84 mg, 29%) as a pale yellow solid: mp 131-134° C.; EI-HRMS m/e calcd for C17H15Cl2N3O (M+) 347.0592, found 347.0594.

Workup

  1. stirringThis solution was stirred at 0° C. for 15 min
  2. temperatureto warm to 25° C. where it
  3. stirringwas stirred for 30 min
  4. stirringwas then stirred at 25° C. for 40 h
  5. customThe organic layer was separated
  6. washwas washed with a saturated aqueous sodium chloride solution (1×25 mL)
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d11747dc51ca41aa90a639dba0e1bc74
Source dataset
uspto-grants-2005_04
Patent number
US06881844B2

Reaction notes

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