Hydrochloric Acid → HCID 59146021, compound

HRID 1512952Notes

Reaction equation

HRID 1512952 reaction equation
[OH-].[K+].[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[C:21]([F:35])[CH:22]=[C:23]4[C:27]=3[NH:26][CH:25]=[C:24]4[CH2:28][CH2:29][C:30]([O:32]CC)=[O:31])[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12].I[CH3:37].[OH-].[Na+].Cl>CS(C)=O.C1COCC1.O>[Cl:3][C:4]1[CH:5]=[C:6]([C:14]2[O:18][N:17]=[C:16]([C:19]3[CH:20]=[C:21]([F:35])[CH:22]=[C:23]4[C:27]=3[N:26]([CH3:37])[CH:25]=[C:24]4[CH2:28][CH2:29][C:30]([OH:32])=[O:31])[N:15]=2)[CH:7]=[N:8][C:9]=1[O:10][CH:11]([CH3:13])[CH3:12]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 14798Sodium HydroxideHCID 59146050HCID 59146050, compound

Product 1

HCID 59146021HCID 59146021, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Potassium hydroxide (90 mg) was added to a solution of ethyl 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1H-indol-3-yl]propanoate (D139) (189 mg) and iodomethane (0.25 mL) in DMSO (3 mL) at RT. The reaction mixture was stirred at RT for 5 hours. Then the reaction was quenched with saturated ammonium chloride, and extracted with EA for 3 times. The combined organic solution was washed with brine and dried over anhydrous sodium sulfate. The dried solution was concentrated to afford the crude product as a yellow oil. This oil was dissolved in THF (3 mL) and water (3 mL). Sodium hydroxide (40 mg) was then added to the mixture. The reaction mixture was stirred at 90° C. for 1 hour, and at RT for another 24 hours. Then 0.5 M HCl was added until pH was about 6. The solvent was concentrated, and the residue was dissolved in water. The precipitated solid was purified by MDAP to afford 3-[7-(5-{5-chloro-6-[(1-methylethyl)oxy]-3-pyridinyl}-1,2,4-oxadiazol-3-yl)-5-fluoro-1-methyl-1H-indol-3-yl]propanoic acid (E102) (112 mg) as an off-white solid. δH (DMSO-d6, 400 MHz): 1.38 (6H, d), 2.58 (2H, t), 2.93 (2H, t), 3.62 (3H, s), 5.42-5.48 (1H, m), 7.29 (1H, s), 7.30 (1H, dd), 7.65 (1H, dd), 8.59 (1H, d), 8.96 (1H, d), 12.13 (1H, br s). δF (DMSO-d6, 376 MHz): −125.6. MS (ES): C22H20ClFN4O4 requires 458; found 459.1 (M+H+).

Workup

  1. customThen the reaction was quenched with saturated ammonium chloride
  2. extractionextracted with EA for 3 times
  3. washThe combined organic solution was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. concentrationThe dried solution was concentrated
  6. customto afford the crude product as a yellow oil
  7. stirringThe reaction mixture was stirred at 90° C. for 1 hour
  8. waitat RT for another 24 hours
  9. concentrationThe solvent was concentrated
  10. dissolutionthe residue was dissolved in water
  11. customThe precipitated solid was purified by MDAP

Sources & evidence

ORD record
ord-7403c322e63b40c08aa6e5df8f9122f6
Source dataset
uspto-grants-2012_07
Patent number
US08217028B2

Reaction notes

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