Triethylamine → 6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3h-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amide

HRID 216531

Reaktionsgleichung

Reaktionsgleichung von HRID 216531
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]2[C:10]([C:19](O)=[O:20])=[CH:11][C:12]3[NH:16][CH:15]=[N:14][C:13]=3[C:17]=2[F:18])=[C:4]([Cl:22])[CH:3]=1.C1C=[CH:25][C:26]2N(O)N=N[C:27]=2[CH:28]=1.C(N(CC)CC)C.Cl.C1([N:44](C)[OH:45])CC1.CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)(=O)C.O>[CH:26]1([CH2:25][O:45][NH:44][C:19]([C:10]2[C:9]([NH:8][C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][C:4]=3[Cl:22])=[C:17]([F:18])[C:13]3[N:14]=[CH:15][NH:16][C:12]=3[CH:11]=2)=[O:20])[CH2:27][CH2:28]1

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 211141586-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acidHCID 21114231Cyclopropyl methyl hydroxylamine hydrochloride

Produkt 1

HCID 98251576-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3h-benzoimidazole-5-carboxylic acid cyclopropylmethoxy-amideAusbeute 89 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

6-(4-Bromo-2-chloro-phenylamino)-7-fluoro-3H-benzoimidazole-5-carboxylic acid 10b (22 mg, 0.057 mmol) is dissolved in DMF (1 mL) and HOBt (9 mg, 0.062 mmol) followed by triethyl amine (18 μL, 0.132 mmol) is added. Cyclopropyl methyl hydroxylamine hydrochloride (8 mg, 0.062 mmol) is added followed by EDCI (14 mg, 0.074 mmol). After 16 hours, the reaction mixture is diluted with ethyl acetate and water and the layers separated. The organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine. The organic layer is dried (MgSO4) and concentrated under reduced pressure to give 23 mg (89%) pure desired product. MS APCI (+) m/z 455, 453 (M+ Br pattern) detected; MS APCI (−) m/z 453, 451 (M− Br pattern) detected; 1H NMR (400 MHz, DMSO-d6) δ 11.69 (broad s, 1H), 8.43 (s, 1H), 7.62 (d, 1H), 7.28 (dd, 1H), 6.42 (m, 1H), 3.63 (d, 2H), 1.03 (m, 1H), 0.48 (m, 2H), 0.19 (m, 2H); 19F NMR (376 MHz, DMSO-d6) −132.95 (s).

Aufarbeitung

  1. additionis added
  2. customthe layers separated
  3. washThe organic layer is washed with saturated NH4Cl, brine, saturated NaHCO3, water and brine
  4. dry with materialThe organic layer is dried (MgSO4)
  5. concentrationconcentrated under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-54c0e4bba6b548f4a6a088a8796cb801
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193230B2

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