4-Methylmorpholine → N-(Tertiarybutoxycarbonyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide

HRID 1589307Notes

Reaction equation

HRID 1589307 reaction equation
[C:1]([NH:8][C@H:9]([C:14]([OH:16])=O)[CH2:10][CH:11]([CH3:13])[CH3:12])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].Cl.C(N=C=NCCCN(C)C)C.CN1CCOCC1.[CH3:36][NH:37][C:38](=[O:50])[C@H:39]([CH2:41][C:42]1[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=1)[NH2:40]>C(Cl)Cl.CN(C=O)C>[CH3:36][NH:37][C:38](=[O:50])[C@H:39]([CH2:41][C:42]1[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=1)[NH:40][C:14](=[O:16])[C@H:9]([CH2:10][CH:11]([CH3:12])[CH3:13])[NH:8][C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 83170L-Leucine, N-((1,1-dimethylethoxy)carbonyl)-HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 14303038O-methyl-L-tyrosine N-Methylamide

Product 1

HCID 18597342N-(Tertiarybutoxycarbonyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of BOC-L-Leucine (5.26 g, 0.021M) in CH2Cl2 (40 ml) and DMF (10 ml) stirred at 0° was added N-ethyl-N'-(3-dimethylaminopropyl)carbodiimide hydrochloride (4 g, 0.021M). After 15 min., N-methyl morpholine (0.021M) was added followed by, after a further 10 min. at 0°, a solution of O-methyl-L-tyrosine N-Methylamide (4.3 g, 0.019M) in CH2Cl2. The reaction mixture was allowed to warm to room temperature and stirred overnight. The reaction was then concentrated in vacuo, and the residue in CH2Cl2, washed in turn with H2O (200 ml), saturated aq. NaHCO3 (200 ml), dilute HCl (1M; 200 ml), saturated aq. NaHCO3 (200 ml) and water (150 ml), dried (Na2SO4) and evaporated in vacuo to a solid. Recrystallisation from ethyl acetate/hexane gave N-(Tertiarybutoxycarbonyl)-L-leucyl-O-methyl-L-tyrosine N-methylamide as a white crystalline solid, (4.5 g), m.p. 159-161; (Found: C, 62.65; H, 8.33; N, 9.96. C22H35N3O5 requires C, 62.69; H, 8.37; N 9.97%). νmax (CDCl3) 3400, 1700 and 1662 cm-1 ; δ(CDCl3) 0.91 (6H, dd, J=7 and 14 Hz, CH(CH3)2); 1.37 (9H, s, OC(CH3)3); 1.47-1.7 (3H, m, CH2CH(CH3)2); 2.71 (3H, d, J=4.7 Hz, NHCH3), 2.98 and 3.14 (each 1H, each m, CH2C6H4); 3.78 (3H, s, OCH3); 4.0 and 4.61 (each 1H, each m, 2×α-CH); 4.86, (1H, br s, OCONH); 6.40 and 6.55 (each 1H, each br s, CONH×2); 6.82 (2H, d, J=8.4 Hz, Tyr H-3 and H-5); 7.08 (2H, d, J=8.4 Hz, Tyr H-2 and H-6); m/e 422 (70%, [m+1]+), 365 (70%, [m-58]+).

Workup

  1. customafter a further 10 min.
  2. customat 0°
  3. concentrationThe reaction was then concentrated in vacuo
  4. washthe residue in CH2Cl2, washed in turn with H2O (200 ml), saturated aq. NaHCO3 (200 ml), dilute HCl (1M; 200 ml), saturated aq. NaHCO3 (200 ml) and water (150 ml)
  5. dry with materialdried (Na2SO4)
  6. customevaporated in vacuo to a solid
  7. customRecrystallisation from ethyl acetate/hexane

Sources & evidence

ORD record
ord-55d7319f6a894bd4bf89c1d2f0e2871b
Source dataset
uspto-grants-1986_02
Patent number
US04568666

Reaction notes

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