1-Hydroxybenzotriazole → 2-[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamide

HRID 1189046Notes

Reaction equation

HRID 1189046 reaction equation
Cl.CN.[CH2:4]([O:6][C:7]1[CH:8]=[C:9]([O:25][C:26]2[CH:27]=[N:28][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:30][CH:31]=2)[CH:10]=[C:11]2[C:15]=1[NH:14][C:13]([C:16]1[S:17][CH:18]([CH2:21][C:22](O)=[O:23])[CH2:19][N:20]=1)=[CH:12]2)[CH3:5].O[N:37]1[C:41]2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O.C(N(CC)CC)C>[CH2:4]([O:6][C:7]1[CH:8]=[C:9]([O:25][C:26]2[CH:27]=[N:28][C:29]([S:32]([CH3:35])(=[O:34])=[O:33])=[CH:30][CH:31]=2)[CH:10]=[C:11]2[C:15]=1[NH:14][C:13]([C:16]1[S:17][CH:18]([CH2:21][C:22]([NH:37][CH3:41])=[O:23])[CH2:19][N:20]=1)=[CH:12]2)[CH3:5]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 6364545Methylamine hydrochlorideHCID 58237023[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid

Product 1

HCID 445168802-[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]-N-methylacetamideYield 99%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To an ice-cooled and stirred mixture of methylamine hydrochloride (26 mg) and triethylamine (0.053 mL) in N,N-dimethylformamide (5 mL) were added [2-(7-ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (90 mg), 1-hydroxybenzotriazole (52 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (73 mg). After stirring at 4° C. to room temperature for 15 h, the reaction mixture was partitioned between ethyl acetate and water. The organic layer was washed successively with aqueous sodium hydrogen carbonate solution and brine, dried (MgSO4), filtered, and concentrated to give a pale yellow amorphous solid, which was crystallized from ethyl acetate-hexane to give the title compound (91 mg, 99%) as pale yellow crystals. MS 489 (MH+). mp 233-235° C.

Workup

  1. stirringAfter stirring at 4° C. to room temperature for 15 h
  2. customthe reaction mixture was partitioned between ethyl acetate and water
  3. washThe organic layer was washed successively with aqueous sodium hydrogen carbonate solution and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a pale yellow amorphous solid, which
  8. customwas crystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-f3f680b49ed14ffd9393aaafb44d184b
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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