Water → 2-[3-(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 343160Notes

Reaction equation

HRID 343160 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](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][CH:52]=[CH:53][CH:54]=2)[N:49]([C:56]([O:58][C:59]([CH3:62])([CH3:61])[CH3:60])=[O:57])[N:48]=1.O>CN(C=O)C.C1(C)C=CC=CC=1>[C:59]([O:58][C:56]([N:49]1[C:50]2[C:55](=[CH:54][CH:53]=[CH:52][CH:51]=2)[C:47]([CH2:46][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][CH:16]=[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:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:4]2=[O:34])=[N:48]1)=[O:57])([CH3:62])([CH3:61])[CH3:60]

Participants

7

Reactant 4

HCID 962WaterHCID 3251421Potassium bis(trimethylsilyl)amideHCID 107900232-(2,4-Dioxo-5-phenyl-2,3,4,5-tetrahydro-benzo[b][1,4]diazepin-1-yl)-N-isopropyl-N-(4-methoxy-phenyl) acetamideHCID 108049513-(Bromomethyl)-1H-indazole, N1-BOC protected

Product 1

HCID 107705992-[3-(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-acetamideYield 68.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

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 311 mg of 3-Bromomethyl-1-tert-butoxycarbonyl indazole, prepared as in Intermediate 1, 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 420 mg of the title compound: 1H NMR (400 MHz, CDCl3) δ8.03 (d, 1H, J=8.3), 7.86 (d, 1H, J=8.0), 7.51-7.18 (m, 14H), 7.10 (m, 1H), 6.94 (m, 1H), 5.02 (m, 1H,J=6.8), 4.32 (dd, 1H, J=8.9, 4.7), 4.24 (d, 1H, J=16.4), 4.22 (d, 1H, J=16.4), 3.85 (dd, 1H, J=16.5, 8.9), 3.53 (dd, 1H, J=16.5, 4.7), 1.64 (s, 9H), 1.07 (d, 6H, J=6.8).

Workup

  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%)

Sources & evidence

ORD record
ord-421f6fd61c394694bfb457a719c3e657
Source dataset
uspto-grants-1999_01
Patent number
US05859007

Reaction notes

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