Triethylamine → HCID 67118561, compound

HRID 1189004Notes

Reaction equation

HRID 1189004 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:30])=[O:29])=[CH:24][N:23]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([OH:20])=O)[CH2:15][N:16]=1)=[CH:8]2.O[N:33]1[C:37]2C=CC=CC=2N=N1.[Cl-].C[NH3+].C(N(CC)CC)C>CN(C)C=O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([O:21][C:22]2[CH:27]=[CH:26][C:25]([S:28]([CH3:31])(=[O:29])=[O:30])=[CH:24][N:23]=2)[CH:6]=[C:7]2[C:11]=1[NH:10][C:9]([C:12]1[S:13][CH:14]([CH2:17][C:18]([NH:33][CH3:37])=[O:20])[CH2:15][N:16]=1)=[CH:8]2

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 11637Methanamine, hydrochloride (1:1)HCID 757711-HydroxybenzotriazoleHCID 67118993HCID 67118993, compound

Product 1

HCID 67118561HCID 67118561, compoundYield 62%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of [2-(7-methoxy-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (280 mg), N-ethyl-N′-(37-dimethylaminopropyl)carbodiimide hydrochloride (233 mg), 1-hydroxybenzotriazole (164 mg), methylammonium chloride (82 mg), triethylamine (0.2 mL) and N,N-dimethylformamide (12 mL) was stirred at room temperature for 5 h. The mixture was concentrated under reduced pressure. The residue was dissolved in water and the mixture was extracted with ethyl acetate-tetrahydrofuran. The organic layer was washed successively with 1M hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by basic silica gel column chromatography (methanol/ethyl acetate/hexane=0/75/25 to 10/90/0, volume ratio) to give a pale yellow amorphous solid. The amorphous solid was crystallized from ethyl acetate-diethyl ether to give white crystals. The crystals were washed with methanol-acetone to give the title compound (178 mg, 62%) as colorless crystals. MS 475 (MH+). mp 207-209° C.

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. dissolutionThe residue was dissolved in water
  3. extractionthe mixture was extracted with ethyl acetate-tetrahydrofuran
  4. washThe organic layer was washed successively with 1M hydrochloric acid, water, saturated aqueous sodium hydrogen carbonate solution and saturated brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by basic silica gel column chromatography (methanol/ethyl acetate/hexane=0/75/25 to 10/90/0, volume ratio)
  9. customto give a pale yellow amorphous solid
  10. customThe amorphous solid was crystallized from ethyl acetate-diethyl ether
  11. customto give white crystals
  12. washThe crystals were washed with methanol-acetone

Sources & evidence

ORD record
ord-b0df6ae5817748b9b10638b69af47499
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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