Thionyl Chloride → HCID 11268205, compound

HRID 1058508Notes

Reaction equation

HRID 1058508 reaction equation
N1([C:4]2[C:5]([N+:22]([O-:24])=[O:23])=[CH:6][C:7]([S:18]([CH3:21])(=[O:20])=[O:19])=[C:8]([CH:17]=2)[C:9]([NH:11][CH2:12][CH:13]([OH:16])[CH2:14][OH:15])=[O:10])CC1.[Cl:25]C1C([N+]([O-])=O)=CC(S(C)(=O)=O)=C(C=1)C(O)=O.O=S(Cl)Cl.NCC(O)CO>CN(C=O)C.O.CCOC(C)=O>[Cl:25][C:4]1[C:5]([N+:22]([O-:24])=[O:23])=[CH:6][C:7]([S:18]([CH3:21])(=[O:20])=[O:19])=[C:8]([CH:17]=1)[C:9]([NH:11][CH2:12][CH:13]([OH:16])[CH2:14][OH:15])=[O:10]

Participants

8

Reactant 4

HCID 24386Thionyl ChlorideHCID 735613-Amino-1,2-propanediolHCID 9863629HCID 9863629, compoundHCID 11288978HCID 11288978, compound

Product 1

HCID 11268205HCID 11268205, compoundYield 91%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-5 °C

Procedure

Preparation of 5-(aziridin-1-yl)-N-(2,3-dihydroxypropyl)-2-(methylsulfonyl)-4-nitrobenzamide (10) A mixture of 5-chloro-2-(methylsulfonyl)-4-nitrobenzoic acid (Somani et al., Br. J. Cancer 1994, 69 (Suppl. XXI), 38) (2.21 g, 7.9 mmol) and SOCl2 (20 mL) containing DMF (2 drops) was refluxed for 1 h, then evaporated to dryness under reduced pressure. The resulting crude acid chloride was dissolved in anhydrous Me2CO (40 mL), and the solution was cooled to −5° C. and treated in one portion with a cold solution of 3-aminopropane-1,2-diol (1.48 g, 1.62 mmol) in water (20 mL). The mixture was shaken at room temperature for 15 min, then diluted with water (20 mL) and concentrated under reduced pressure to ca. 30 mL. After addition of solid NaCl, the mixture was extracted with EtOAc (3x), and the extracts were worked up to give a solid. This was dissolbed in EtOAc and filtered through a column of silica gel to give 5-chloro-N-(2,3-dihydroxypropyl)-2-(methylsulfonyl)-4-nitrobenzamide (2.54 g, 91%), mp (EtOAc/iPr2O) 141-142° C. 1NMR [(CD3)2SO] δ8.83 (t, J=5.7 Hz, 1H, NH), 8.55 (s, 1 , H-3), 8.08 (s, 1H, H-6), 4.81 (d, J=5.0 Hz, 1H, CHOH), 4.55 (t, J=5.8 Hz, 1H, CH2OH), 3.70-3.58 (m, 1H, CHOH), 3.45 (s, 3H, CH3), 3.44-3.35 (m, 3H, CH2OH & CONHCHH), 3.17-3.06 (m, 1H, CONHCHH). Anal. Calcd for C11H13ClN2O7S: C, 3 71; N, 7.94; S, 9.09 Found: C, 37.73;H, 3.96; N, 7.83; S, 9.29%.

Workup

  1. temperaturewas refluxed for 1 h
  2. customevaporated to dryness under reduced pressure
  3. dissolutionThe resulting crude acid chloride was dissolved in anhydrous Me2CO (40 mL)
  4. concentrationconcentrated under reduced pressure to ca. 30 mL
  5. additionAfter addition of solid NaCl
  6. extractionthe mixture was extracted with EtOAc (3x)
  7. customto give a solid
  8. filtrationfiltered through a column of silica gel

Sources & evidence

ORD record
ord-f44ca9079419444cb460c42a9a37bbb6
Source dataset
uspto-grants-2003_02
Patent number
US06517836B1

Reaction notes

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