1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 2-[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamide

HRID 1189047Notes

Reaction equation

HRID 1189047 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:22][C:23]2[CH:24]=[N:25][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][CH:28]=2)[CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]([CH2:18][C:19]([OH:21])=O)[CH2:16][N:17]=1)=[CH:9]2)[CH3:2].[NH4+].O[N:35]1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C>CN(C)C=O>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([O:22][C:23]2[CH:24]=[N:25][C:26]([S:29]([CH3:32])(=[O:31])=[O:30])=[CH:27][CH:28]=2)[CH:7]=[C:8]2[C:12]=1[NH:11][C:10]([C:13]1[S:14][CH:15]([CH2:18][C:19]([NH2:35])=[O:21])[CH2:16][N:17]=1)=[CH:9]2)[CH3:2]

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220338091-Hydroxybenzotriazole, ammonium saltHCID 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 582371072-[2-(7-Ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetamideYield 88.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To an ice-cooled and stirred mixture of [2-(7-ethoxy-5-{[6-(methylsulfonyl)pyridin-3-yl]oxy}-1H-indol-2-yl)-4,5-dihydro-1,3-thiazol-5-yl]acetic acid (95 mg) in N,N-dimethylformamide (5 mL) were added 1-hydroxybenzotriazole ammonium salt (61 mg) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (77 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 (84 mg) as colorless crystals. Recrystallization from ethyl acetate-hexane gave the title compound (71 mg, 76%) as colorless crystals. MS 475 (MH+). mp 195-196° 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-ef5a4cefab954d97a5c232dbafa7317a
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

Loading…