1-Hydroxybenzotriazole → HCID 136331244, compound

HRID 1958812Notes

Reaction equation

HRID 1958812 reaction equation
[CH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[C:10]([CH3:12])[CH:11]=1)[C:6]([OH:8])=O)=[O:2].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[CH2:35]([C:37]1[CH:38]=[C:39]([CH:44]=[C:45]([CH3:48])[C:46]=1[OH:47])[C:40]([NH:42]O)=[NH:41])[CH3:36]>CN(C=O)C>[CH2:35]([C:37]1[CH:38]=[C:39]([C:40]2[N:41]=[C:6]([C:5]3[CH:4]=[C:3]([CH:11]=[C:10]([CH3:12])[CH:9]=3)[CH:1]=[O:2])[O:8][N:42]=2)[CH:44]=[C:45]([CH3:48])[C:46]=1[OH:47])[CH3:36]

Participants

6

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 197881733-Formyl-5-methylbenzoic acidHCID 178436626HCID 178436626, compound

Product 1

HCID 136331244HCID 136331244, compoundYield 28.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 3-formyl-5-methyl-benzoic acid (3.80 g, 23.2 mmol), HOBt (4.17 g, 27.8 mmol) and EDC HCl (4.44 g, 23.2 mmol) in DMF (200 mL) was stirred at rt for 5 min before 3-ethyl-4,N-dihydroxy-5-methyl-benzamidine (4.50 g, 23.2 mmol) was added. The mixture was stirred at rt for 1 h. The mixture was heated to 75° C. and stirring was continued for 3 h. The mixture was concentrated to about 40 mL, acidified by adding formic acid (0.6 mL), diluted with a small amount of acetonitrile/water and separated by prep. HPLC (Waters XBridge Prep C18, 50×50 mm+50×100 mm, 10 μm, 80% to 10% water (containing 0.5% of formic acid) in MeCN) to give the title compound as a white solid (2.14 g). LC-MS**: tR=0.82 min; [M+1]+=323.15, 1H NMR (D6-DMSO): δ 1.20 (t, J=7.3 Hz, 3H), 2.28 (s, 3H), 2.55 (s, 3H), 2.69 (q, J=7.5 Hz, 2H), 7.71 (d, J=2.0 Hz, 2H), 8.05 (s, 1H), 8.32 (s, 1H), 8.49 (s, 1H), 8.95 (s, 1H), 10.14 (s, 1H).

Workup

  1. additionwas added
  2. temperatureThe mixture was heated to 75° C.
  3. stirringstirring
  4. waitwas continued for 3 h
  5. concentrationThe mixture was concentrated to about 40 mL
  6. additionby adding formic acid (0.6 mL)
  7. additiondiluted with a small amount of acetonitrile/water
  8. customseparated by prep

Sources & evidence

ORD record
ord-82df7354a75b44bb84735f8ffa2b6dd8
Source dataset
uspto-grants-2013_04
Patent number
US08410151B2

Reaction notes

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