m-Tolyl isocyanate → HCID 57309341, compound

HRID 2379313Notes

Reaction equation

HRID 2379313 reaction equation
C1([C:7]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:18])[C:10](=[O:19])[CH:9]([NH:20][C:21]([O:23]CC3C=CC=CC=3)=O)[N:8]=2)CCCCC1.[C:31]1([CH3:40])[CH:36]=[CH:35][CH:34]=[C:33]([N:37]=C=O)[CH:32]=1>C(O)=O.CO.[Pd].O1CCCC1>[CH2:12]1[CH2:17][CH:16]([C:9]2([NH:20][C:21]([NH:37][C:33]3[CH:34]=[CH:35][CH:36]=[C:31]([CH3:40])[CH:32]=3)=[O:23])[N:8]=[CH:7][C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]([CH3:18])[C:10]2=[O:19])[CH2:15][CH2:14][CH2:13]1

Participants

6

Reactant 2

HCID 69303m-Tolyl isocyanateHCID 152352853(R,S)-[(Benzyloxycarbonyl)amino]-5-cydohexyl-1,3-dihydro-1-methyl-2H-1,4-benzodiazepin-2-one

Product 1

HCID 57309341HCID 57309341, compoundYield 41.2%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 8028TetrahydrofuranSolventHCID 18963719Formic acid methanolSolvent2×

Procedure

5-Cyclohexyl-1,3-dihydro-1-methyl-3(R,S)-[(benzyloxycarbonyl)amino]-2H-1,4-benzodiazepin-2-one (0.34 g, 0.84 mmol) was dissolved in formic acid/methanol (50 ml of a 4.5% (v/v) solution), and added, over 5 min, to a stirred suspension of 10% palladium on carbon (100 mg, 30% (w/w)) in formic acid/methanol (10 ml of a 4.5% (v/v)) solution). After 45 min the catalyst was filtered off and washed sequentially with methanol and acetone. The flitrate was evaporated in vacuo and the residue partitioned between ethyl acetate (100 ml) and 10% sodium carbonate solution (100 ml). The organic phase was separated, dried (Na2SO4) and evaporated to give a clear oil, which was used without further purification. A solution of the crude amine (167 mg, 0.61 mmol) in anhydrous tetrahydrofuran (10 ml) was treated with m-tolylisocyanate (79 μl, 0.61 mmol) dropwise over 5 min. After stirring at ambient temperature for 1.5 h the solvent was removed under reduced pressure to leave a white solid. The solid was recrystallised from methanol to give the urea (70 mg, 28%) as a white solid. mp 207°-209° C. 1H NMR (360 MHz, CDCl3) δ 1.07-2.04 (10H, m), 2.29 (3H, s), 2.79 (1H, m), 3.40 (3H, m), 5.40 (1H, d, J=8 Hz), 6.71 (1H, d, J=8 Hz), 6.84 (2H, m), 7.07-7.30 (5H, m), 7.55 (2H, m).

Workup

  1. filtrationAfter 45 min the catalyst was filtered off
  2. washwashed sequentially with methanol and acetone
  3. customThe flitrate was evaporated in vacuo
  4. customthe residue partitioned between ethyl acetate (100 ml) and 10% sodium carbonate solution (100 ml)
  5. customThe organic phase was separated
  6. dry with materialdried (Na2SO4)
  7. customevaporated
  8. customto give a clear oil, which
  9. customwas used without further purification
  10. customwas removed under reduced pressure
  11. customto leave a white solid
  12. customThe solid was recrystallised from methanol

Sources & evidence

ORD record
ord-636578ce68b24487a76fc9c31a5dbc75
Source dataset
uspto-grants-1994_11
Patent number
US05360802

Reaction notes

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