Triethylamine → Ethyl 3-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-tetrahydropyran-4-yloxy-acetyl]amino]thiazol-5-yl]oxybenzoate

HRID 524423Notes

Reaction equation

HRID 524423 reaction equation
[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([O:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:14](O)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:3][CH2:2]1.[NH2:24][C:25]1[S:26][C:27]([O:30][C:31]2[CH:32]=[C:33]([CH:39]=[CH:40][CH:41]=2)[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:28][N:29]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.C(N(CC)CC)C>ClCCl.O>[CH:1]1([S:4]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]([O:17][CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[C:14]([NH:24][C:25]3[S:26][C:27]([O:30][C:31]4[CH:32]=[C:33]([CH:39]=[CH:40][CH:41]=4)[C:34]([O:36][CH2:37][CH3:38])=[O:35])=[CH:28][N:29]=3)=[O:15])=[CH:9][CH:8]=2)(=[O:6])=[O:5])[CH2:2][CH2:3]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 59610020(4-Cyclopropanesulfonyl-phenyl)-[(tetrahydro-pyran-4-yloxy)]-acetic acidHCID 86669549Ethyl 3-(2-aminothiazol-5-yl)oxybenzoate

Product 1

HCID 86669551Ethyl 3-[2-[[2-(4-cyclopropylsulfonylphenyl)-2-tetrahydropyran-4-yloxy-acetyl]amino]thiazol-5-yl]oxybenzoateYield 58%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
25 °C

Procedure

A 1 L two necked round bottom flask maintained under inert atmosphere was charged with 2-(4-cyclopropylsulfonylphenyl)-2-tetrahydropyran-4-yloxy-acetic acid (16 g, 47 mmol; preparation 4), ethyl 3-(2-aminothiazol-5-yl)oxybenzoate (13.6 g, 51 mmol; preparation 20), HOBt (7.6 g, 56 mmol) and EDCl (10.8 g, 56 mmol) in Dichloromethane (500 mL). The reaction mixture was stirred at 25° C. and added triethylamine (15.8 mL, 113 mmol). The resulting mixture was continued to stir for 16 hours at 25° C. Completion of reaction was confirmed by TLC. The reaction mixture was diluted with water (400 mL) and DCM (250 mL). The layers were separated. The aqueous layer was again extracted with DCM (2×200 mL). The combined organic layer was washed with 1N HCl (300 mL), brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure. The obtained residue was purified by column chromatography using 5-40% ethyl acetate in hexanes as solvent system to get a pure product (16 g).

Workup

  1. stirringto stir for 16 hours at 25° C
  2. customCompletion of reaction
  3. customThe layers were separated
  4. extractionThe aqueous layer was again extracted with DCM (2×200 mL)
  5. washThe combined organic layer was washed with 1N HCl (300 mL), brine
  6. dry with materialdried over anhydrous sodium sulphate
  7. concentrationconcentrated under reduced pressure
  8. customThe obtained residue was purified by column chromatography

Sources & evidence

ORD record
ord-d08e902b3af94fea9e93a72535d295bb
Source dataset
uspto-grants-2016_05
Patent number
US09340506B2

Reaction notes

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