Acetic Anhydride → HCID 131721083, compound

HRID 343229Notes

Reaction equation

HRID 343229 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH2:11][CH:12]3[C:18](=[O:19])[N:17]([CH2:20][C:21]([N:23]([C:27]4[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=4)[CH:24]([CH3:26])[CH3:25])=[O:22])[C:16]4[CH:34]=[CH:35][CH:36]=[CH:37][C:15]=4[N:14]([C:38]4[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=4)[C:13]3=[O:44])=[N:7][NH:8]2)=[CH:4][CH:3]=1.[C:45](OC(=O)C)(=[O:47])[CH3:46]>>[C:45]([N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=2)[C:6]([CH2:11][CH:12]2[C:18](=[O:19])[N:17]([CH2:20][C:21]([N:23]([C:27]3[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=3)[CH:24]([CH3:25])[CH3:26])=[O:22])[C:16]3[CH:34]=[CH:35][CH:36]=[CH:37][C:15]=3[N:14]([C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[C:13]2=[O:44])=[N:7]1)(=[O:47])[CH3:46]

Participants

3

Reactant 2

HCID 7918Acetic AnhydrideHCID 178457888HCID 178457888, compound

Product 1

HCID 131721083HCID 131721083, compound

Procedure

300 mg (0.505 mmol) 2-[3-(6-Fluoro-1H-indazol-3-ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5,-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-(4-fluoro-phenyl)-N-isopropyl-acetamide, prepared as in Example 63, is dissolved in 15 mL Acetic anhydride and heated at reflux 1 h. The solvent is removed in vacuo and the residue purified by preparative HPLC on a Delta-Pak C-18 column eluted from 35% to 60% CH3CN in H2O with 0.1% TFA buffer over 30 minutes at 150 mL/min. The appropriate fraction is frozen and lyophilized to give 144 mg (0.226 mmol) of the title compound as a white lyophilizate: 1H NMR (CDCl3, 300 MHz) δ8.04 (m, 1H), 7.76 (m, 1H), 7.50 (d, 1H, J=8.0), 7.39-7.08 (m, 12H), 6.98 (d, 1H, J=7.8), 5.02 (m, 1H), 4.32 (d, 1H, J=16.6), 4.30 (t, 1H), 4.10 (d, 1H, J=16.6), 3.75 (m, 1H), 3.57 (m, 1H), 2.63 (s, 3H), 1.08 (m, 6H); low resolution MS (FAB) m/e 636.1 (MH+); TLC Rf =0.30 (EtOAc/Hexanes, 1:2).

Workup

  1. temperatureheated
  2. temperatureat reflux 1 h
  3. customThe solvent is removed in vacuo
  4. customthe residue purified by preparative HPLC on a Delta-Pak C-18 column
  5. washeluted from 35% to 60% CH3CN in H2O with 0.1% TFA buffer over 30 minutes at 150 mL/min
  6. temperatureThe appropriate fraction is frozen

Sources & evidence

ORD record
ord-6747be8c234a461c845f2d5e51478d32
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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