1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 1-({4-[(2-Fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)-3-(hydroxymethyl)azetidin-3-ol

HRID 1809013Notes

Reaction equation

HRID 1809013 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:15]([OH:17])=O)=[CH:12][S:13][CH:14]=1.Cl.CN(C)CCCN=C=NCC.Cl.[OH:31][CH2:32][C:33]1([OH:37])[CH2:36][NH:35][CH2:34]1>CN(C)C1C=CN=CC=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[C:11]([C:15]([N:35]2[CH2:36][C:33]([CH2:32][OH:31])([OH:37])[CH2:34]2)=[O:17])=[CH:12][S:13][CH:14]=1

Participants

6

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 552884783-(Hydroxymethyl)azetidin-3-ol hydrochlorideHCID 666174654-[(2-Fluoro-4-iodophenyl)amino]thiophene-3-carboxylic acid

Product 1

HCID 670515741-({4-[(2-Fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)-3-(hydroxymethyl)azetidin-3-olYield 106.8%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

4-[(2-fluoro-4-iodophenyl)amino]thiophene-3-carboxylic acid (200 mg, 0.551 mmol), 4-(dimethylamino)pyridine (202 mg, 1.65 mmol) and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (127 mg, 0.662 mmol) were dissolved in DMF (3 mL). The mixture was stirred at ambient for 5 minutes and then 3-(hydroxymethyl)azetidin-3-ol hydrochloride (72 mg, 0.516 mmol) was added and the mixture was stirred for 15 h. The mixture was partitioned between ethyl acetate and 20% citric acid. The aqueous portion was extracted with ethyl acetate. The combined organic portion was washed with 5% lithium chloride, saturated sodium bicarbonate and brine, then was dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was crystallized from dichloromethane to afford 1-({4-[(2-fluoro-4-iodophenyl)amino]-3-thienyl}carbonyl)-3-(hydroxymethyl)azetidin-3-ol (247 mg, 0.551 mmol, quantitative yield) as off-white crystals: MS (EI) for C15H14FIN2O3S: 449 (MH+).

Workup

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

Sources & evidence

ORD record
ord-ea60359c3ddf4a93bcf712ca33b49eed
Source dataset
uspto-grants-2013_01
Patent number
US08362002B2

Reaction notes

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