Diisopropylethylamine → (5S)-5-({[6-(2-Cyclopropylpyrimidin-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}methyl)-5-methylimidazolidine-2,4-dione

HRID 1441483Notes

Reaction equation

HRID 1441483 reaction equation
[CH3:1][C@@:2]1([CH2:9][S:10](Cl)(=[O:12])=[O:11])[C:6](=[O:7])[NH:5][C:4](=[O:8])[NH:3]1.[CH:14]1([C:17]2[N:22]=[CH:21][C:20]([C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[CH2:29][NH:28][CH2:27][CH2:26]4)=[CH:19][N:18]=2)[CH2:16][CH2:15]1.CCN(C(C)C)C(C)C>C1COCC1.O.[Cl-].[Na+].O>[CH:14]1([C:17]2[N:18]=[CH:19][C:20]([C:23]3[CH:24]=[C:25]4[C:30](=[CH:31][CH:32]=3)[CH2:29][N:28]([S:10]([CH2:9][C@@:2]3([CH3:1])[NH:3][C:4](=[O:8])[NH:5][C:6]3=[O:7])(=[O:12])=[O:11])[CH2:27][CH2:26]4)=[CH:21][N:22]=2)[CH2:16][CH2:15]1

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 16738713(4S)-(4-methyl-2,5-dioxoimidazolidin-4-yl)methanesulphonyl chlorideHCID 667348536-[2-(Cyclopropyl)pyrimidin-5-yl]-1,2,3,4-tetrahydroisoquinoline

Product 1

HCID 59164389(5S)-5-({[6-(2-Cyclopropylpyrimidin-5-yl)-3,4-dihydroisoquinolin-2(1H)-yl]sulfonyl}methyl)-5-methylimidazolidine-2,4-dioneYield 54.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 23713072Sodium chloride dihydrateSolvent

Procedure

[(4S)-4-Methyl-2,5-dioxoimidazolidin-4-yl]methanesulfonyl chloride (0.020 g, 0.087 mmol) in anhydrous THF (0.40 mL) was added dropwise to a stirred solution of 6-[2-(cyclopropyl)pyrimidin-5-yl]-1,2,3,4-tetrahydroisoquinoline (0.023 g, 0.091 mmol), DIPEA (0.022 mL, 0.13 mmol) and dry THF (0.50 mL) at RT. After the addition was complete, the solution was stirred at RT for 2 h and then taken up in water-brine and extracted twice with EtOAc. The combined organic phases were washed with brine, dried, filtered and concentrated to give a crude product. Purification by preparative HPLC afforded 0.021 g (50%) of the title compound as a white solid.

Workup

  1. additionAfter the addition
  2. extractionextracted twice with EtOAc
  3. washThe combined organic phases were washed with brine
  4. customdried
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customto give a crude product
  8. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-fecda251a1884e5aa75e4b466a604b18
Source dataset
uspto-grants-2010_02
Patent number
US07655664B2

Reaction notes

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