StartseiteMCPWorkbenchSkills
StartseiteWorkbenchBenachrichtigungenMein Bereich
llms.txt · MCP-AnleitungDatenschutz · Nutzungsbedingungen · Supportv1.8.0
  1. Startseite
  2. /Reaktion

3-(Bromomethyl)-1-methyl-1H-indazole → N-Isopropyl-N-(4-methoxy-phenyl)-2-[3-(1-methyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]acetamide

HRID 343217
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 343217
[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]([O:19][CH3:20])=[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.[CH3:35][N:36]1[C:44]2[C:39](=[CH:40][CH:41]=[CH:42][CH:43]=2)[C:38]([CH2:45]Br)=[N:37]1>CN(C=O)C.C1(C)C=CC=CC=1>[CH:21]([N:12]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=1)[C:10](=[O:11])[CH2:9][N:8]1[C:2](=[O:1])[CH:3]([CH2:45][C:38]2[C:39]3[C:44](=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:36]([CH3:35])[N:37]=2)[C:4](=[O:34])[N:5]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)[C:6]2[CH:27]=[CH:26][CH:25]=[CH:24][C:7]1=2)([CH3:23])[CH3:22]
KomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

5

Edukt 2

HCID 107755483-(Bromomethyl)-1-methyl-1H-indazoleHCID 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 10555571N-Isopropyl-N-(4-methoxy-phenyl)-2-[3-(1-methyl-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]acetamideAusbeute 22,8 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140
Toluene
Lösungsmittel
HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

To a stirring solution of 330 mg (0.73 mmol) 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, prepared as in Intermediate 4, in 10 mL DMF at 0° C. is added dropwise over 5 min 1.75 mL (0.87 mmol, 1.1 equiv) of a 0.5M solution of KN(TMS)2 in toluene. The resulting solution is stirred 10 min, then a solution of 180 mg (1.18 mmol, 1.1 equiv) of 1-methyl-3-bromomethyl-1H-indazole in 3 mL DMF is added. The resulting solution is stirred 3 h at RT and then quenched with 5 mL of H2O. The reaction mixture is poured into 50 mL of EtOAc and extracted with H2O (2×50 mL). The organic layer is separated, dried (MgSO4), and the solvents removed in vacuo. Purification by silica gel flash column chromatography using hexane/EtOAc 2/1 as eluent followed by further purification via silica gel MPLC using a Si60 column and hexane/EtOAc 1/1 as eluent followed by lyophilization in acetonitrile/H2O afforded 100 mg of the title compound as a white amorphous solid: 1H NMR (CDCl3, 300 MHz) δ7.74 (d, 1H, J=8.3), 7.25-6.76 (m, 16H), 4.85 (m, 1H), 4.11 (s, br, 2H), 3.97 (dd, 1H, J=5.6, 7.8), 3.77 (s, 3H), 3.70 (s, 3H), 3.63 (dd, 1H, J=7.8, 15.9), 3.48 (dd, 1H, J=5.6, 15.9), 0.92 (d, 6H, J=6.8); low resolution MS (FAB)m/e 602 (MH+), 437. Anal. (C36H35N5O4) Calcd. C, 71.86; H, 5.86; N, 11.64; Found C, 71.69; H, 5.91; N, 11.56.

Aufarbeitung

  1. stirringThe resulting solution is stirred 3 h at RT
  2. customquenched with 5 mL of H2O
  3. additionThe reaction mixture is poured into 50 mL of EtOAc
  4. extractionextracted with H2O (2×50 mL)
  5. customThe organic layer is separated
  6. dry with materialdried (MgSO4)
  7. customthe solvents removed in vacuo
  8. customPurification by silica gel flash column chromatography
  9. customfollowed by further purification via silica gel MPLC

Quellen und Nachweise

ORD-Eintrag
ord-4962be34ea9640d38fe5723588cb21b3
Quelldatensatz
uspto-grants-1999_01
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US05859007

Notizen zur Reaktion

Wird geladen…

Auf dieser SeiteKomponentenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion