1-Hydroxybenzotriazole → HCID 178497653, compound

HRID 412724Notes

Reaction equation

HRID 412724 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH2:15][C:14]2[NH:17][C:18]([CH:20]([C:22]3[N:23]([CH3:34])[C:24]4[CH:30]=[C:29]([C:31](O)=[O:32])[CH:28]=[CH:27][C:25]=4[N:26]=3)[CH3:21])=[N:19][C:13]=2[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:35][CH2:36][CH2:37][O:38][C:39]1[CH:48]=[CH:47][CH:46]=[CH:45][C:40]=1[C:41]([O:43][CH3:44])=[O:42].C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C>C(Cl)CCl.CN(C=O)C>[CH3:44][O:43][C:41]([C:40]1[CH:45]=[CH:46][CH:47]=[CH:48][C:39]=1[O:38][CH2:37][CH2:36][NH:35][C:31]([C:29]1[CH:28]=[CH:27][C:25]2[N:26]=[C:22]([CH:20]([C:18]3[NH:17][C:14]4[CH2:15][CH2:16][N:11]([C:9]([O:8][CH2:1][C:2]5[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=5)=[O:10])[CH2:12][C:13]=4[N:19]=3)[CH3:21])[N:23]([CH3:34])[C:24]=2[CH:30]=1)=[O:32])=[O:42]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531Diisopropylethylamine3×HCID 14273287HCID 14273287, compoundHCID 178437536HCID 178437536, compound

Product 1

HCID 178497653HCID 178497653, compoundYield 67.7%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
20 °C

Procedure

A mixture comprising 2-[1-(5-benzyloxycarbonyl-4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridin-2-yl)ethyl]-3-methyl-3H-benzoimidazole-5-carboxylic acid (0.75 g, 1.6 mmol), DMF (6.5 mL), methyl 2-(2-aminoethoxy)benzoate (0.38 g, 1.6 mmol) and HOBT (0.22 g, 1.6 mmol) was cooled under nitrogen to −40° C., treated with EDC (0.32 g, 1.6 mmol) and N,N-diisopropylethylamine (0.29 mL, 1.6 mmol) and 15 minutes later with additional N,N-diisopropylethylamine (0.29 mL), allowed to warm to 20° C. and stirred for 16 hours. The mixture then was cooled to −40° C., treated with additional EDC (0.080 g) and N,N-diisopropylethylamine (0.050 mL), stirred for 15 minutes at −40° C. and 2 hours at 20° C. and concentrated by shortpath distillation. The residue was partitioned between chloroform and sodium bicarbonate and the organic layer was washed with sodium chloride, 0.5M potassium sulfate and sodium chloride, dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was purified by silica gel chromatography (CHCl3/MeOH/AcOH: 95/5/1) to provide benzyl 2-(1-{6-[2-(2-methoxycarbonylphenoxy)ethylcarbamoyl]-1-methyl-1H-benzoimidazol-2-yl}ethyl)-1,4,6,7-tetrahydroimidazo[4,5-c]pyridine-5-carboxylate (0.69 g, 66%) as a glassy brown foam; 1H-NMR (300 MHz, DMSO-d6) d ppm: 11.92 (s, 1H), 8.49 (t, 1H, J=5.0 Hz), 8.02 (s, 1H), 7.69 (d, 1H, J=9.9 Hz), 7.60 (m, 2H), 7.50 (t, 1H, J=8.3 Hz), 7.30 (m, 5H), 7.19 (d, 1H, J=9.9 Hz), 6.99 (t, 1H, J=8.3 Hz), 5.04 (s, 2H), 4.61 (q, 1H, J=8.8 Hz), 4.30 (br s, 2H), 4.20 (t, 2H, J=5.0 Hz), 3.74 (s, 3H), 3.68 (s, 3H), 3.63 (m, 4H), 2.55 (br s, 2H), 1.67 (d, 3H, J=8.8 Hz).

Workup

  1. temperatureThe mixture then was cooled to −40° C.
  2. stirringstirred for 15 minutes at −40° C. and 2 hours at 20° C.
  3. concentrationconcentrated by shortpath distillation
  4. customThe residue was partitioned between chloroform and sodium bicarbonate
  5. washthe organic layer was washed with sodium chloride, 0.5M potassium sulfate and sodium chloride
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel chromatography (CHCl3/MeOH/AcOH: 95/5/1)

Sources & evidence

ORD record
ord-18f886bdd93844de90bdaa2e7de1366a
Source dataset
uspto-grants-2003_05
Patent number
US06562854B2

Reaction notes

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