2-Fluorobenzoic acid → N-(4-Chloro-5-(1-(4-chlorophenyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-3-yl)-2-fluorobenzyl)-2-fluorobenzamide

HRID 59537

반응식

HRID 59537 반응식
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[NH2:15][CH2:16][C:17]1[C:18]([F:37])=[CH:19][C:20]([Cl:36])=[C:21]([C:23]2[NH:24][C:25](=[O:35])[N:26]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[N:27]=2)[CH:22]=1.CCN(C(C)C)C(C)C>C1COCC1.CN(C=O)C>[Cl:36][C:20]1[C:21]([C:23]2[NH:24][C:25](=[O:35])[N:26]([C:28]3[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=3)[N:27]=2)=[CH:22][C:17]([CH2:16][NH:15][C:4](=[O:6])[C:3]2[CH:7]=[CH:8][CH:9]=[CH:10][C:2]=2[F:1])=[C:18]([F:37])[CH:19]=1

참가 물질

7

반응물 4

HCID 99352-Fluorobenzoic acidHCID 24386Thionyl ChlorideHCID 81531DiisopropylethylamineHCID 1366448485-(5-(aminomethyl)-2-chloro-4-fluorophenyl)-2-(4-chlorophenyl)-2H-1,2,4-triazol-3 (4H)-one

생성물 1

HCID 136246041N-(4-Chloro-5-(1-(4-chlorophenyl)-4,5-dihydro-5-oxo-1H-1,2,4-triazol-3-yl)-2-fluorobenzyl)-2-fluorobenzamide수율 9.5%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

실험 절차

A mixture of 2-fluoro benzoic acid (0.400 g), thionyl chloride (20 mL) and DMF (cat. amt.) was refluxed for 5 h and excess of solvent was removed under reduced pressure to obtain crude product. The obtained crude product was added to the solution of 5-(5-(aminomethyl)-2-chloro-4-fluorophenyl)-2-(4-chlorophenyl)-2H-1,2,4-triazol-3 (4H)-one (Intermediate-78, 0.250 g) and DIPEA (1.0 mL) in THF (20 mL) and the reaction mass was stirred for 3 h. After completion of reaction, reaction mass was quenched with water and extracted with ethyl acetate. The organic layer was separated, concentrated to afford 0.032 g of the desired product. 1H NMR (300 MHz, DMSO): δ 4.53 (br s, 2H), 7.29 (m, 2H), 7.70 (m, 3H), 7.78 (m, 3H), 7.95 (br s, 2H), 8.94 (br s, 1H), 12.63 (br s, 1H); MS (m/z): 475.39 (M+H)+.

후처리

  1. temperaturewas refluxed for 5 h and excess of solvent
  2. customwas removed under reduced pressure
  3. customto obtain crude product
  4. customThe obtained crude product
  5. customAfter completion of reaction, reaction mass
  6. customwas quenched with water
  7. extractionextracted with ethyl acetate
  8. customThe organic layer was separated
  9. concentrationconcentrated

출처 및 근거

ORD 기록
ord-aaa69057702d4e17bd5a5c8ee6c701e5
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09439890B2

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