Dimethylformamide → HCID 54613686, compound

HRID 573374Notes

Reaction equation

HRID 573374 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([NH:13][C:14]2[N:22]=[CH:21][CH:20]=[CH:19][C:15]=2[C:16]([OH:18])=O)[CH:6]=[C:7]([O:11][CH3:12])[C:8]=1[O:9][CH3:10].CN(C=O)C.C(N=C=NCCCN(C)C)C.[NH2:39][C:40]1[S:41][C:42]2[CH:48]=[C:47]([F:49])[CH:46]=[CH:45][C:43]=2[N:44]=1>>[F:49][C:47]1[CH:46]=[CH:45][C:43]2[N:44]=[C:40]([NH:39][C:16](=[O:18])[C:15]3[CH:19]=[CH:20][CH:21]=[N:22][C:14]=3[NH:13][C:5]3[CH:6]=[C:7]([O:11][CH3:12])[C:8]([O:9][CH3:10])=[C:3]([O:2][CH3:1])[CH:4]=3)[S:41][C:42]=2[CH:48]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 3199542-Amino-6-fluorobenzothiazoleHCID 14222041HCID 14222041, compound

Product 1

HCID 54613686HCID 54613686, compound

Conditions

Temperature
27 °C

Procedure

Compound 13 (185 mg, 1 mmol) and 3,4,5-methoxy aniline (20, 183 mg, 1 mmol) was taken in ethylene glycol and refluxed at 160° C. for 6 h. Then the reaction mixture was cooled and extracted in ethyl acetate (4×25 mL) from the aqueous layer and concentrated in vacuo. The compound was further purified by column chromatography using 60-120 silica gel (ethyl acetate/hexane, 1:9) to obtain Ethyl 2-(3,4,5-trimethoxy anilino) nicotinate (27) as pure product. Ethyl2-(3,4,5-trimethoxy anilino) nicotinate (27, 332 mg, 1 mmol) were refluxed with 2N NaOH in ethanol for 2 h. The reaction mixture was cooled and left acidified with 2N HCl white solids obtained, filtered and washed with water to give pure compound of 2-(3,4,5-trimethoxyphenylamino) nicotinic acid (34). To a stirred solution of 2-(3,4,5-trimethoxyphenylamino) nicotinic acid (34, 244 mg, 1 mmol) in dry DMF (10 mL) hydroxy benzotriazole HOBt (1.2 mmol) were added at 0° C. After 10 min 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDCI) (1.2 mmol) was added and finally 2-amino 6-fluoro benzothiazole (36, 117 mg, 0.7 mmol) were added Then the resulting mixture was stirred at room temperature (27° C.) for 8-10 h and then the reaction mixture was quenched with NaHCO3 and extracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer and dried over anhydrous Na2SO4. The resulting product (11) was purified by column chromatography employing EtOAc/Hexane as an eluent.

Workup

  1. customthe reaction mixture was quenched with NaHCO3
  2. extractionextracted in ethyl acetate (4×25 mL) from the ice cold aqueous layer
  3. dry with materialdried over anhydrous Na2SO4
  4. customThe resulting product (11) was purified by column chromatography

Sources & evidence

ORD record
ord-31d5c7c153534d419193d2f147f65b0e
Source dataset
uspto-grants-2015_05
Patent number
US09029553B2

Reaction notes

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