Ethyl Acetate → HCID 67051573, compound

HRID 1808987Notes

Reaction equation

HRID 1808987 reaction equation
[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])=[C:4]([CH:8]=[CH:9][C:10]=1[F:11])[C:5]([OH:7])=O.Cl.CN(C)CCCN=C=NCC.Cl.[OH:34][CH:35]([C:37]1([OH:41])[CH2:40][NH:39][CH2:38]1)[CH3:36].C(OCC)(=O)C>CN(C)C1C=CN=CC=1.CN(C=O)C>[F:1][C:2]1[C:3]([NH:12][C:13]2[CH:18]=[CH:17][C:16]([I:19])=[CH:15][C:14]=2[F:20])=[C:4]([C:5]([N:39]2[CH2:40][C:37]([CH:35]([OH:34])[CH3:36])([OH:41])[CH2:38]2)=[O:7])[CH:8]=[CH:9][C:10]=1[F:11]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 220256632-(2-Fluoro-4-iodoanilino)-3,4-difluorobenzoic acidHCID 67051864HCID 67051864, compound

Product 1

HCID 67051573HCID 67051573, compoundYield 65.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent2×

Procedure

3,4-Difluoro-2-[(2-fluoro-4-iodophenyl)amino]benzoic acid (362 mg, 0.921 mmol), prepared using procedures similar to those described in U.S. Pat. No. 7,019,033, 4-(dimethylamino)pyridine (337 mg, 2.76 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (212 mg, 1.11 mmol) were dissolved in DMF (3 mL). The mixture was stirred at ambient for 5 minutes and then 3-(1-hydroxyethyl)azetidin-3-ol hydrochloride (0.922 mmol) in DMF (2 mL) was added and the mixture was stirred for 15 h. The mixture was partitioned between ethyl acetate and 5% lithium chloride. The organic portion was washed with 20% citric acid, saturated sodium bicarbonate and brine, then was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. Column chromatography (silica gel, 80% ethyl acetate in hexanes) gave 1-({3,4-difluoro-2-[(2-fluoro-4-iodophenyl)amino]phenyl}carbonyl)-3-(1-hydroxyethyl)azetidin-3-ol (296 mg, 0.602 mmol, 65% yield): MS (EI) for C18H16F3IN2O3: 493 (MH+).

Workup

  1. stirringthe mixture was stirred for 15 h
  2. customThe mixture was partitioned between ethyl acetate and 5% lithium chloride
  3. washThe organic portion was washed with 20% citric acid, saturated sodium bicarbonate and brine
  4. dry with materialwas dried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ad1f49634b8944b2b21d049610899f6b
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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