Diisopropylethylamine → HCID 68603208, compound

HRID 643491Notes

Reaction equation

HRID 643491 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7](C(=O)C(F)(F)F)[CH2:6][CH2:5]2.BrC1C=CC=C2C=1CN(C(=O)C(F)(F)F)CC2.CCN(C(C)C)C(C)C.[CH3:44][C@@:45]1([CH2:52][S:53](Cl)(=[O:55])=[O:54])[C:49](=[O:50])[NH:48][C:47](=[O:51])[NH:46]1>C(O)C.[OH-].[NH4+].C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH2:8][N:7]([S:53]([CH2:52][C@@:45]1([CH3:44])[NH:46][C:47](=[O:51])[NH:48][C:49]1=[O:50])(=[O:54])=[O:55])[CH2:6][CH2:5]2

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 16738713(4S)-(4-methyl-2,5-dioxoimidazolidin-4-yl)methanesulphonyl chlorideHCID 231554111-(6-bromo-3,4-dihydroisoquinolin-2(1H)-yl)-2,2,2-trifluoroethanoneHCID 59463166HCID 59463166, compound

Product 1

HCID 68603208HCID 68603208, compoundYield 113.9%

Reagents, catalysts & solvents 3

HCID 14923Ammonium HydroxideCatalystHCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A 3:1 mixture (0.44 g, 1.4 mmol) of 6-bromo-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline and 8-bromo-2-(trifluoroacetyl)-1,2,3,4-tetrahydroisoquinoline (prepared according to Tetrahedron Lett. 1996, 37(31), 5453-5456) was stirred in ethanol (10 mL) containing a few drops of 25% ammonium hydroxide at RT. After 2.5 h, the solution was concentrated, dissolved in dry THF (1.0 mL) under argon and cooled on an ice-bath. DIPEA (0.41 mL, 2.4 mmol) was added followed by a solution of [(4S)-4-methyl-2,5-dioxoimidazolidin-4-yl]methanesulfonyl-chloride (0.27 g, 1.2 mmol) and dry THF (1.0 mL). The mixture was stirred at RT for 1 h and then concentrated. The crude product was taken up in water and extracted twice with EtOAc. The combined organic phases were washed with brine, dried, filtered and concentrated to give 0.55 g of a mixture of (5S)-5-({[6-bromo-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}methyl)-5-methylimidazolidine-2,4-dione and (5S)-5-({[8-bromo-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}methyl)-5-methylimidazolidine-2,4-dione. The regioisomers were separated by preparative HPLC.

Workup

  1. concentrationthe solution was concentrated
  2. dissolutiondissolved in dry THF (1.0 mL) under argon
  3. temperaturecooled on an ice-bath
  4. concentrationconcentrated
  5. extractionextracted twice with EtOAc
  6. washThe combined organic phases were washed with brine
  7. customdried
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-5646a36493da4da3be43b78d4fa64c41
Source dataset
uspto-grants-2010_04
Patent number
US07700604B2

Reaction notes

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