Water → HCID 67368676, compound

HRID 1753129Notes

Reaction equation

HRID 1753129 reaction equation
[Si:1]([O:8][CH2:9][C:10]1[N:14]([CH2:15][C:16]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=O)[C:13]([C:25](O)=[O:26])=[CH:12][CH:11]=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[CH2:28]([NH2:31])[CH2:29][NH2:30].C(Cl)Cl.O>ClCCCl>[Si:1]([O:8][CH2:9][C:10]1[N:14]2[CH2:15][C:16]3([C:18]4[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=4)[NH:31][CH2:28][CH2:29][N:30]3[C:25](=[O:26])[C:13]2=[CH:12][CH:11]=1)([C:4]([CH3:6])([CH3:5])[CH3:7])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 3301EthylenediamineHCID 6344DichloromethaneHCID 67367602HCID 67367602, compound

Product 1

HCID 67368676HCID 67368676, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-1-[2-(4-chlorophenyl)-2-oxoethyl]-1H-pyrrole-2-carboxylic acid (˜70% pure, 268 mg, 0.46 mmol) was stirred at reflux in 1,2-dichloroethane with ethane-1,2-diamine (938 mL) for 18 h. The resultant suspension was concentrated in vacuo to give a residue. The mixture was treated with CH2Cl2 (30 mL) and water (30 mL) to form an emulsion that was filtered through a filter system. The organic layer was then separated. The aqueous layer was extracted with further CH2Cl2 (2×30 mL). The combined organic layers were dried (MgSO4), filtered and concentrated in vacuo to give a waxy solid. Purification by flash column chromatography (Biotage SP4, 4 g cartridge, 0-5% MeOH gradient in CH2Cl2) gave 8-({[tert-butyl(dimethyl)silyl]oxy}methyl)-10a-(4-chlorophenyl)-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]-pyrazin-5-one as a off-white solid (85%, yield 42%). 1H NMR (400 MHz, MeOD): δ−0.11 (s, 3H), −0.04 (s, 3H), 0.79 (s, 9H), 2.79 (dt, 1H, J 12.2, 8.2 Hz), 3.32-3.37 (m, 1H), 3.51 (ddd, 1H, J 11.0, 7.9, 3.1 Hz), 3.71-3.79 (m, 1H), 4.20 (d, 1H, J 12.5 Hz), 4.44 (d, 1H, J 13.2 Hz), 4.56 (d, 1H, J 13.2 Hz), 4.76 (d, 1H, J 12.5 Hz), 6.05 (d, 1H, J 3.8 Hz), 6.77 (d, 1H, J 3.8 Hz), 7.25-7.35 (m, 4H).

Workup

  1. concentrationThe resultant suspension was concentrated in vacuo
  2. customto give a residue
  3. customto form an emulsion that
  4. filtrationwas filtered through a filter system
  5. customThe organic layer was then separated
  6. extractionThe aqueous layer was extracted with further CH2Cl2 (2×30 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto give a waxy solid
  11. customPurification by flash column chromatography (Biotage SP4, 4 g cartridge, 0-5% MeOH gradient in CH2Cl2)

Sources & evidence

ORD record
ord-1324c58a43f343dd88c4817bbb5db766
Source dataset
uspto-grants-2015_10
Patent number
US09163029B2

Reaction notes

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