Water → HCID 69063025, compound

HRID 1295062Notes

Reaction equation

HRID 1295062 reaction equation
S(Cl)(Cl)=O.[CH2:5]([N:12]1[C:19]2[CH:18]3[CH2:20][CH:17]3[CH2:16][C:15]=2[C:14]([C:21]([NH2:23])=O)=[N:13]1)[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1.C([O-])(O)=O.[Na+].O>CN(C=O)C>[CH2:5]([N:12]1[C:19]2[CH:18]3[CH2:20][CH:17]3[CH2:16][C:15]=2[C:14]([C:21]#[N:23])=[N:13]1)[C:6]1[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 962WaterHCID 24386Thionyl Chloride3×HCID 516892Sodium BicarbonateHCID 69061130HCID 69061130, compound

Product 1

HCID 69063025HCID 69063025, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent4×

Conditions

Temperature
0 °C

Procedure

A flask equipped with a drying tube under N2 atmosphere was charged with anhydrous DMF (50 mL). The flask was cooled to 0° C. and thionyl chloride (4.84 mL, 66.5 mmol) was added dropwise over a period of 2 min. After stirring for an additional 10 min, a suspension of 2-benzyl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carboxylic acid amide, (14.0 g, 55.3 mmol) in DMF (90 mL) was added over 5 min using an addition funnel. The mixture was slowly warmed to rt and stirred for 20 min at which time additional thionyl chloride (3.05 mL, 41.9 mmol) was added as a pre-mixed solution in DMF (20 mL). The reaction was stirred for an additional 20 min and a second pre-mixed solution of thionyl chloride (6.0 mL, 82.5 mmol) in DMF (20 mL) was added. The reaction was stirred for an additional 15 min and NaHCO3 (sat. aq., 50 mL) was added followed by H2O (100 mL). The mixture was stirred for 10 min and concentrated to near dryness in vacuo. The residue was diluted with EtOAc (350 mL) and H2O (250 mL). The layers were separated and the aqueous phase was back-extracted with EtOAc (250 mL). The combined organics were washed with NaHCO3 (sat. aq., 400 mL), and brine (400 mL), dried over MgSO4, filtered, and concentrated to give 2-benzyl-1a,2,5,5a-tetrahydro-1H-2,3-diaza-cyclopropa[a]pentalene-4-carbonitrile as a brown solid. 1H NMR (400 MHz, CDCl3): δ 7.37 (3H, m), 7.25 (2H, m), 5.31 (1H, d, J=14.8 Hz), 5.24 (1H, d, J=14.8 Hz), 2.86, (1H, dd, J=16.4, 6.4 Hz), 2.72 (1H, d, J=16.0 Hz), 2.19 (1H, m), 1.87 (1H, m), 1.07 (1H, m), 0.32 (1H, m). 13C APT NMR (100 MHz, CDCl3): δ up: 154.4, 135.3, 130.0, 118.9, 114.3, 55.9, 26.2, 16.9; down: 129.2, 128.6, 128.1, 24.2, 14.4. HPLC/MS: Discovery® C18 column (5μ, 50×2.1 mm), 5% v/v CH3CN (containing 1% v/v TFA) in H2O (containing 1% v/v TFA) gradient to 99% v/v CH3CN in H2O, 0.75 mL/min, tr=2.23 min, ESI+=236.1 (M+H).

Workup

  1. customA flask equipped with a drying tube under N2 atmosphere
  2. additionwas added over 5 min
  3. temperatureThe mixture was slowly warmed to rt
  4. stirringThe reaction was stirred for an additional 20 min
  5. stirringThe reaction was stirred for an additional 15 min
  6. stirringThe mixture was stirred for 10 min
  7. concentrationconcentrated
  8. additionThe residue was diluted with EtOAc (350 mL) and H2O (250 mL)
  9. customThe layers were separated
  10. extractionthe aqueous phase was back-extracted with EtOAc (250 mL)
  11. washThe combined organics were washed with NaHCO3 (sat. aq., 400 mL), and brine (400 mL)
  12. dry with materialdried over MgSO4
  13. filtrationfiltered
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-cf3707c81e654327aeaa128f19192735
Source dataset
uspto-grants-2007_07
Patent number
US07241792B2

Reaction notes

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