1-Hydroxybenzotriazole → HCID 59469185, compound

HRID 1809038Notes

Reaction equation

HRID 1809038 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:11]([C:18]([OH:20])=O)=[N:12][N:13]([CH3:17])[C:14](=[O:16])[CH:15]=1.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.[OH:43][C:44]1([C@@H:48]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH3:49])[CH2:47][NH:46][CH2:45]1>CN(C=O)C.C(N(CC)CC)C>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[C:11]([C:18]([N:46]2[CH2:47][C:44]([C@@H:48]([NH:50][C:51](=[O:57])[O:52][C:53]([CH3:56])([CH3:55])[CH3:54])[CH3:49])([OH:43])[CH2:45]2)=[O:20])=[N:12][N:13]([CH3:17])[C:14](=[O:16])[CH:15]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 594691014-(2-Fluoro-4-iodophenylamino)-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acidHCID 86621276HCID 86621276, compound

Product 1

HCID 59469185HCID 59469185, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8471TriethylamineSolvent

Procedure

To a suspension of 4-[(2-fluoro-4-iodophenyl)amino]-1-methyl-6-oxo-1,6-dihydropyridazine-3-carboxylic acid (50 mg, 0.13 mmol) in DMF (2 mL), prepared using similar procedures to those described in Reference 4, at room temperature was added 1-hydroxybenzotriazole (36.3 mg, 0.27 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (52 mg, 0.27 mmol) and the reaction was stirred for 2 hours. 1,1-Dimethylethyl [(1S)-1-(3-hydroxyazetidin-3-yl)ethyl]carbamate (30 mg, 0.13 mmol), prepared using procedures similar to those in Example 28, and triethylamine (0.04 mL) were added and the mixture was stirred for 15 hours. The reaction mixture was partitioned between saturated sodium chloride and ethyl acetate. The organic layer was washed with 5% lithium chloride solution, saturated sodium bicarbonate, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to give crude product as yellow oil. The oil was purified by column chromatography (silica gel, ethyl acetate) to afford 1,1-dimethylethyl {(1S)-1-[1-({4-[(2-fluoro-4-iodophenyl)amino]-1-methyl-6-oxo-1,6-dihydropyridazin-3-yl}carbonyl)-3-hydroxyazetidin-3-yl]ethyl}carbamate as a yellow oil (55 mg, 73% yield): 1H NMR (400 MHz, CDCl3): 10.24-10.23 (m, 1H), 7.52-7.50 (m, 2H), 7.12-7.07 (m, 1H), 6.10-6.09 (m, 1H), 5.13-5.09 (m, 1H), 4.91-4.82 (m, 1H), 4.60-4.39 (m, 2H), 4.10-4.08 (m, 1H), 4.00-3.87 (m, 2H), 3.70 (d, 3H), 1.43 (s, 9H), 1.24-1.20 (m, 3H); MS (EI) for C22H27FIN5O5: 588 (MH+).

Workup

  1. customprepared
  2. customthose described in Reference 4, at room temperature
  3. additionwere added
  4. stirringthe mixture was stirred for 15 hours
  5. customThe reaction mixture was partitioned between saturated sodium chloride and ethyl acetate
  6. washThe organic layer was washed with 5% lithium chloride solution, saturated sodium bicarbonate
  7. dry with materialdried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give crude product as yellow oil
  11. customThe oil was purified by column chromatography (silica gel, ethyl acetate)

Sources & evidence

ORD record
ord-a88d9df5a6a146929a202c123ff463fd
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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