Water → 2-[3-(6-Fluoro-1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamide

HRID 343161Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 343161
[O:1]=[C:2]1[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]2[CH:18]=[CH:17][C:16](OC)=[CH:15][CH:14]=2)=[O:11])[C:7]2[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=2[N:5]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:4](=[O:34])[CH2:3]1.C[Si]([N-][Si](C)(C)C)(C)C.[K+].Br[CH2:46][C:47]1[C:55]2[C:50](=[CH:51][C:52]([F:56])=[CH:53][CH:54]=2)[N:49]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[N:48]=1.O>CN(C=O)C.C1(C)C=CC=CC=1>[F:56][C:52]1[CH:51]=[C:50]2[C:55]([C:47]([CH2:46][CH:3]3[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)=[O:11])[C:7]4[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=4[N:5]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)[C:4]3=[O:34])=[N:48][N:49]2[C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])=[CH:54][CH:53]=1

Komponenten

7

Edukt 4

HCID 962WaterHCID 3251421Potassium bis(trimethylsilyl)amideHCID 10568325Tert-butyl 3-(bromomethyl)-6-fluoro-1H-indazole-1-carboxylateHCID 107900232-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide

Produkt 1

HCID 677004612-[3-(6-Fluoro-1-tert-butoxycarbonyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-phenyl-acetamideAusbeute 65 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 427 mg of 2-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamide in 5 mL of dry DMF at 0° C. is added 2.2 mL of a 0.5M solution of potassium bis(trimethylsilyl)amide in toluene. The reaction mixture is stirred for 30 min at 0° C. and a solution of 329 mg of 3-Bromomethyl-6-fluoro-1-tert-butoxycarbonyl indazole in 2 mL of dry DMF is added dropwise. The reaction mixture is stirred overnight at RT, poured into water and the product extracted with ethyl acetate (2×15 mL). The solvent is removed in vacuo and the residue is purified by silica gel flash column chromatography (MeOH 1%:CHCl3 99%) to afford 410 mg of the title compound: 1H NMR (400 MHz, CDCl3) δ7.85-6.91 (m, 17H), 5.01 (m, 1H,J=6.8), 4.22 (m, 3H), 3.81 (dd, 1H, J=16.5, 8.9), 3.51 (dd, 1H, J=16.5, 4.7), 1.68 (s, 9H), 1.07 (d, 6H, J=6.8).

Aufarbeitung

  1. stirringThe reaction mixture is stirred overnight at RT
  2. extractionthe product extracted with ethyl acetate (2×15 mL)
  3. customThe solvent is removed in vacuo
  4. customthe residue is purified by silica gel flash column chromatography (MeOH 1%:CHCl3 99%)

Quellen und Nachweise

ORD-Eintrag
ord-2a2f21ace2e54e7982f492890e063539
Quelldatensatz
uspto-grants-1999_01
Patentnummer
US05859007

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