1,8-Diazabicyclo(5.4.0)undec-7-ene → HCID 69517337, compound

HRID 853820Notes

Reaction equation

HRID 853820 reaction equation
[N-:1]=[C:2]=[O:3].C(N([CH:10]([CH3:12])[CH3:11])CC)(C)C.[ClH:13].[NH2:14][CH:15]([CH2:20][NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[C:16]([O:18]C)=O.[CH2:29]1[CH2:39]CN2[C:32](=[N:33]CCC2)[CH2:31][CH2:30]1>C(Cl)Cl>[C:25]([O:24][C:22](=[O:23])[NH:21][CH2:20][CH:15]1[C:16](=[O:18])[N:1]([C:39]2[CH:29]=[CH:30][C:31]([C:32]#[N:33])=[C:12]([Cl:13])[C:10]=2[CH3:11])[C:2](=[O:3])[NH:14]1)([CH3:28])([CH3:27])[CH3:26]

Participants

6

Reactant 4

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 81531DiisopropylethylamineHCID 105034IsocyanateHCID 18388108H-Dap(boc)-ome hcl

Product 1

HCID 69517337HCID 69517337, compoundYield 85.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of the isocyanate of Example 4E (1.60 g, 8.33 mmol) in CH2Cl2 (40 mL) was added 4 Å molecular sieves (˜0.5 g), followed by diisopropylethylamine (1.74 mL, 9.99 mmol) and methyl 2-amino-3-[(tert-butyloxycarbonyl)amino]-propanoate hydrochloride (2.33 g, 9.16 mmol) and the resulting mixture was stirred at rt for 1 h. DBU (1.50 mL, 9.99 mmol) was added and the mixture stirred at rt overnight. Additional DBU (0.37 mL, 2.47 mmol) was then added and the mixture stirred at rt for 5 h. The mixture was then filtered and the solid washed with CH2Cl2. The filtrate was washed with water and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography (silica gel, CH2Cl2/CH3OH, 98:2 to 80:20 gradient) to afford the title compound (2.71 g) as a beige foam. 1H NMR (CDCl3) δ 1.44 (s, 9H), 2.28, 2.29 (s, 3H), 3.56-3.60 (m, 1H), 3.68-3.78 (m, 1H), 4.32-4.35 (m, 1H), 5.02, 5.08 (br s, 1H), 6.63 (br s, 1H), 7.20, 7.25 (d, J=8.3 Hz, 1H), 7.62, 7.63 (d, J=8.3 Hz, 1H); HPLC a) column: Phenominex C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold, 4 mL/min, UV detection at 220 nm, 3.00 min retention time; HPLC b) column: Shimadzu Shim-Pack VP-ODS C18 4.6×50 mm, 4 min gradient, 10% MeOH/90% H2O/0.1% TFA to 90% MeOH/10% H2O/0.1% TFA, 1 min hold, 4 mL/min, UV detection at 220 nm, 2.89 min retention time (99%); HPLC c) column: Daicel Chiralcel OD 4.6×250 mm, Isocratic 25% isopropanol/hexanes, 30 min, 1 mL/min, UV detection at 220 nm, 22.26 min retention time (99%); MS (ES) m/z 377 [M−H]−.

Workup

  1. stirringthe mixture stirred at rt overnight
  2. stirringthe mixture stirred at rt for 5 h
  3. filtrationThe mixture was then filtered
  4. washthe solid washed with CH2Cl2
  5. washThe filtrate was washed with water and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by flash chromatography (silica gel, CH2Cl2/CH3OH, 98:2 to 80:20 gradient)

Sources & evidence

ORD record
ord-67bee85d38234730a8f2215372eb6008
Source dataset
uspto-grants-2007_08
Patent number
US07256208B2

Reaction notes

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