Triethylamine → HCID 67051596, compound

HRID 1672978Notes

Reaction equation

HRID 1672978 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[CH:11]=[N:12][CH:13]=[CH:14][C:15]=1[C:16]([OH:18])=O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[OH:48][C:49]1([C@@H:53]2[CH2:58][CH2:57][CH2:56][CH2:55][N:54]2[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])[CH2:52][NH:51][CH2:50]1>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([I:8])[CH:5]=[CH:4][C:3]=1[NH:9][C:10]1[CH:11]=[N:12][CH:13]=[CH:14][C:15]=1[C:16]([N:51]1[CH2:52][C:49]([C@@H:53]2[CH2:58][CH2:57][CH2:56][CH2:55][N:54]2[C:59]([O:61][C:62]([CH3:65])([CH3:64])[CH3:63])=[O:60])([OH:48])[CH2:50]1)=[O:18]

Participants

7

Reactant 5

HCID 8471Triethylamine2×HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 590267913-((2-Fluoro-4-iodophenyl)amino)isonicotinic acidHCID 67051727HCID 67051727, compound

Product 1

HCID 67051596HCID 67051596, compoundYield 105%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-[(2-Fluoro-4-iodophenyl)amino]pyridine-4-carboxylic acid (200 mg, 0.559 mmol), prepared using procedures similar to those described in WO 2006/045514, was suspended in DMF (7 mL) and 1-hydroxybenzotriazole (151 mg, 1.12 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (214 mg, 1.12 mmol) were added. The mixture was stirred at ambient for 10 minutes and then triethylamine (0.078 mL, 0.559 mmol) was added. After a further 20 minutes, 1,1-dimethylethyl (2S)-2-(3-hydroxyazetidin-3-yl)piperidine-1-carboxylate (143 mg, 0.559 mmol), prepared using similar procedures to those described in Example 22(a) and 22(b), and triethylamine (0.16 mL, 1.15 mmol) were added and the mixture was stirred for 15 hours. The mixture was partitioned between ethyl acetate and saturated ammonium chloride. The organic portion was washed with 5% lithium chloride and twice with saturated sodium bicarbonate, then was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by column chromatography (silica gel, 60-80% ethyl acetate in hexanes) to give 1,1-dimethylethyl (2S)-2-[1-({3-[(2-fluoro-4-iodophenyl)amino]pyridin-4-yl}carbonyl)-3-hydroxyazetidin-3-yl]piperidine-1-carboxylate (368 mg, 0.587 mmol, 74% yield): 1H NMR (400 MHz, CDCl3): 8.73 (br m, 1H), 8.62 (br s, 1H), 8.14 (d, 1H), 7.47 (dd, 1H), 7.43-7.39 (m, 1H), 7.20-7.12 (m, 2H), 4.38-4.21 (m, 2H), 4.16-4.01 (m, 2H), 4.01-3.88 (m, 1H), 3.44-3.30 (m, 1H), 2.98-2.83 (m, 1H), 2.00-1.88 (m, 1H), 1.71-1.50 (m, 6H), 1.44 (s, 9H); MS (EI) for C25H30FIN4O4: 597 (MH+).

Workup

  1. waitAfter a further 20 minutes
  2. additionwere added
  3. stirringthe mixture was stirred for 15 hours
  4. customThe mixture was partitioned between ethyl acetate and saturated ammonium chloride
  5. washThe organic portion was washed with 5% lithium chloride and twice with saturated sodium bicarbonate
  6. dry with materialwas dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe residue was purified by column chromatography (silica gel, 60-80% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-b720a2e73e414a2589f1da6e6ac4a5b7
Source dataset
uspto-grants-2011_08
Patent number
US07999006B2

Reaction notes

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