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 1809013ノート

反応式

HRID 1809013 の反応式
[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

参加物

6

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 142844-(Dimethylamino)pyridine触媒HCID 6228Dimethylformamide溶媒

実験手順

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+).

後処理

  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

出典と根拠

ORDレコード
ord-ea60359c3ddf4a93bcf712ca33b49eed
出典データセット
uspto-grants-2013_01
特許番号
US08362002B2

反応ノート

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