HCID 10754143, compound → 2-[3-(2-Benzyl-5-methyl-2H-pyrazol-3ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamide

HRID 343224Notes

Reaction equation

HRID 343224 reaction equation
[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.[CH2:35]([N:42]1[C:46]([CH2:47]Br)=[CH:45][C:44]([CH3:49])=[N:43]1)[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CN(C=O)C.C1(C)C=CC=CC=1>[CH2:35]([N:42]1[C:46]([CH2:47][CH:3]2[C:2](=[O:1])[N:8]([CH2:9][C:10]([N:12]([CH:21]([CH3:23])[CH3:22])[C:13]3[CH:18]=[CH:17][C:16]([O:19][CH3:20])=[CH:15][CH:14]=3)=[O:11])[C:7]3[CH:24]=[CH:25][CH:26]=[CH:27][C:6]=3[N:5]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:4]2=[O:34])=[CH:45][C:44]([CH3:49])=[N:43]1)[C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1

Participants

5

Reactant 2

HCID 10754143HCID 10754143, compoundHCID 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

Product 1

HCID 867536032-[3-(2-Benzyl-5-methyl-2H-pyrazol-3ylmethyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl]-N-isopropyl-N-(4-methoxy-phenyl)-acetamideYield 60%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×

Procedure

To a stirring solution of 300 mg (0.66 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 5 mL of DMF at 0° C. is added 1.57 mL (0.79 mmol, 1.2 equiv) of a 0.5M solution of KN(TMS)2 in toluene. The resulting solution is stirred 5 min, and a solution of 190 mg (0.72 mmol, 1.1 equiv.) of 1-Benzyl-5-bromomethyl-3-methyl-1H-pyrazole, prepared as in Intermediate 56, in 2 mL of DMF is added. The resulting solution is stirred for 18 h at RT 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 1/2 as eluent afforded 254 mg of the title compound as a white solid: mp 117°-120° C.; 1H NMR (CDCl3, 400 MHz) δ7.37-7.02 (m, 15H), 6.94 (m, 2H), 6.85 (d, 1H, J=7.4), 5.80(s, 1H), 5.30 (dd, 2H, J=16.1, 30.9), 4.98 (m, 1H), 4.19 (dd, 2H, J=15.6, 76.0), 3.83 (s, 3H), 3.43 (t, 1H, J=6.7), 3.25 (ddd, 1H, J=7.1, 16.0, 40.5), 2.20 (s, 3H), 1.06 (m, 6H); low resolution MS (FAB)m/e 642 (MH+), 641 (M+); Anal. (C39H39N5O4) Calcd. C, 72.99; H, 6.13; N, 10.91 Found C, 72.86; H, 6.11; N, 10.96.

Workup

  1. stirringThe resulting solution is stirred for 18 h at RT
  2. customthen quenched 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

Sources & evidence

ORD record
ord-0457a1fa49e34e2089a9d610b1150a06
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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