Diisopropylethylamine → HCID 86758836, compound

HRID 1058854Notes

Reaction equation

HRID 1058854 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C@H:9]([NH:15][C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.Cl[C:24]1[C:33]2[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:27]=[CH:26][N:25]=1.C(N(CC)C(C)C)(C)C>C(OCCO)C>[C:19]([O:18][C:16]([NH:15][C@@H:9]([CH2:8][C:5]1[CH:4]=[CH:3][C:2]([NH:1][C:24]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:27]=[CH:26][N:25]=2)=[CH:7][CH:6]=1)[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[O:17])([CH3:21])([CH3:20])[CH3:22]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 140539Isoquinoline, 1-chloro-HCID 10638537Ethyl 4-amino-N-(tert-butoxycarbonyl)-L-phenylalaninate

Product 1

HCID 86758836HCID 86758836, compound

Reagents, catalysts & solvents 1

HCID 8076Glycol monoethyl etherSolvent

Procedure

A stirred solution of ethyl (S)-3-(4-aminophenyl)-2-(N-t-butyloxycarbonylamino)propanoate (3.08 g, 10.0 mmol), 1-chloroisoquinoline (1.80 g, 11.0 mmol) and N,N-diisopropylethylamine (1.42 g, 1.91 ml, 11.0 mmol) in 2-ethoxyethanol (1.0 ml) was heated at 130° for 4 h. The volatiles were removed in vacuo and the residue partitioned between EtOAc (120 ml) and saturated aqueous NaHCO3 (50 ml). The phases were separated and the aqueous layer was re-extracted with EtOAc (80 ml). The combined organic extracts were washed with brine (30 ml), dried (MgSO4) and evaporated in vacuo. The obtained dark oil was chromatographed (silica; 20-30% EtOAc/hexane) to afford the title compound as a pink oil which crystallised on standing (2.78 g, 64%). δH (CDCl3) 8.07 (1H, d, J 5.8 Hz), 7.93 (1H, d, J 8.4 Hz), 7.72 (1H, d, J 7.5 Hz), 7.63 (1H, d), 7.61 (2H, d, J 8.5 Hz), 7.51 (1H, t, J 6.8 Hz), 7.23 (1H, br s), 7.10 (1H, br s), 7.10 (2H, d, J 6.8 Hz), 5.02 (1H, br d, J 8.0 Hz), 4.54 (1H, br m), 4.16 (2H, t, J 7.1 Hz), 3.05 (2H, br m), 1.43 (9H, s), 1.25 (3H, t, J 7.1 Hz); m/z (ES+, 60V) 436 (MH+).

Workup

  1. customThe volatiles were removed in vacuo
  2. customthe residue partitioned between EtOAc (120 ml) and saturated aqueous NaHCO3 (50 ml)
  3. customThe phases were separated
  4. extractionthe aqueous layer was re-extracted with EtOAc (80 ml)
  5. washThe combined organic extracts were washed with brine (30 ml)
  6. dry with materialdried (MgSO4)
  7. customevaporated in vacuo
  8. customThe obtained dark oil was chromatographed (silica; 20-30% EtOAc/hexane)

Sources & evidence

ORD record
ord-fbb4136d28644e259df0706ac37fd5fa
Source dataset
uspto-grants-2003_02
Patent number
US06518283B1

Reaction notes

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