4-Methylmorpholine → N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{(3-(1H-tetrazol-1-yl)-phenyl]oxy}acetamide

HRID 1809145ノート

反応式

HRID 1809145 の反応式
[N:1]1([C:6]2[CH:7]=[C:8]([CH:14]=[CH:15][CH:16]=2)[O:9][CH2:10][C:11]([OH:13])=O)[CH:5]=[N:4][N:3]=[N:2]1.Cl.C(N=C=NCCCN(C)C)C.ON1C2C=CC=CC=2N=N1.CN1CCOCC1.[NH2:46][C:47]1[CH:48]=[CH:49][C:50]([Cl:57])=[C:51]([C:53]([F:56])([F:55])[F:54])[CH:52]=1>C(OCC)(=O)C.CN(C=O)C>[Cl:57][C:50]1[CH:49]=[CH:48][C:47]([NH:46][C:11](=[O:13])[CH2:10][O:9][C:8]2[CH:14]=[CH:15][CH:16]=[C:6]([N:1]3[CH:5]=[N:4][N:3]=[N:2]3)[CH:7]=2)=[CH:52][C:51]=1[C:53]([F:54])([F:55])[F:56]

参加物

8

反応物 5

HCID 79724-MethylmorpholineHCID 675744-Chloro-3-(trifluoromethyl)anilineHCID 757711-HydroxybenzotriazoleHCID 863916[3-(1H-tetrazol-1-yl)phenoxy]acetic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

生成物 1

HCID 4714043N-[4-chloro-3-(trifluoromethyl)phenyl]-2-{(3-(1H-tetrazol-1-yl)-phenyl]oxy}acetamide

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a 25 mL recovery flask was added 3-tetrazol-1-ylphenoxyacetic acid 3 (200 mg, 0.908 mmol, 1.0 eq.) and a stirbar. 1-Ethyl-3-(3′-dimethylaminopropyl)carbodiimide hydrochloride (261 mg, 1.36 mmol, 1.5 eq.) and 1-hydroxybenzotriazole (184 mg, 1.36 mmol, 1.5 eq.) were added to the flask. DMF (10 mL) and N-methylmorpholine (300 μL, 2.72 mmol, 3.0 eq.) were added to the reaction flask. The mixture was allowed to stir for 30 min at room temperature. 5-amino-2-chlorobenzotrifluoride (355 mg, 1.82 mmol, 2.0 eq.) was added to the flask and the resulting mixture was allowed to stir overnight at room temperature. The reaction mixture was diluted with ethyl acetate (100 mL) and washed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL), and sat'd aq. NaCl (1×50 mL). The aqueous phases were combined and extracted with ethyl acetate (2×30 mL). The combined organic phases were dried over anhydrous Na2SO4, filtered, and concentrated to yield an off-white solid, which did not require further purification (165 mg, 46%). LC/MSD (HP Series 1100 MSD) MS (ES+) m/z 398.0 (M+H)+1 1H-NMR, Varian 400 MHz (DMSO-d6) δ 10.55 (bs, 1H), 10.09 (s, 1H), 8.22 (d, 1H), 7.93-7.91 (m, 1H), 7.68 (d, 1H), 7.61-7.51 (m, 3H), 7.21-7.18 (m, 1H), 4.88 (s, 2H) ppm.

後処理

  1. stirringto stir overnight at room temperature
  2. washwashed with a succession of H2O (1×50 mL), 10% aq. LiCl (3×50 mL)
  3. extractionextracted with ethyl acetate (2×30 mL)
  4. dry with materialThe combined organic phases were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto yield an off-white solid, which
  8. custompurification (165 mg, 46%)

出典と根拠

ORDレコード
ord-3cd356782e1548c8b29e58a21cb16aa0
出典データセット
uspto-grants-2013_01
特許番号
US08362017B2

反応ノート

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