L-Tryptophan, methyl ester → (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl ester

HRID 553066Notes

Reaction equation

HRID 553066 reaction equation
[CH2:1]([O:8][C:9](=[O:38])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:15](=[O:37])[CH2:16][CH2:17][C:18](=[O:36])[C@@H:19]([NH:27][C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)C1C=CC=CC=1.C(N[C@@H](CC1C=CC=CC=1)C(=O)CCC(O)=O)(=O)C1C=CC=CC=1.COC(=O)[C@H](CC1[C:77]2[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=2)[NH:71]C=1)N.O.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[CH3:1][O:8][C:9](=[O:38])[C@H:10]([CH2:14][C:13]1[C:77]2[C:72](=[CH:73][CH:74]=[CH:75][CH:76]=2)[NH:71][CH:12]=1)[NH:11][C:15](=[O:37])[CH2:16][CH2:17][C:18](=[O:36])[C@@H:19]([NH:27][C:28](=[O:35])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

8

Reactant 6

HCID 77980L-Tryptophan, methyl esterHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 17747952HCID 17747952, compoundHCID 57956922HCID 57956922, compound

Product 1

HCID 67163963(5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl esterYield 90%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The experimental procedure employed for the synthesis of (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-proline benzyl ester was followed using the free acid compound 4 (200 mg, 0.6109 mmol, 1.0 eq.), L-tryptophan methyl ester (133 mg, 0.6109 mmol, 1.0 eq.), 1-Hydroxybenzotriazole hydrate (HOBt) (83 mg, 0.6109 mmol, 1.0 eq.), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl) (117 mg, 0.6109 mmol, 1.0 eq.), iPr2NEt (0.11 mL, 0.6110 mmol, 1.0 eq.) and dry DMF/CH2Cl2 (2:8 ratio)(10 mL). Work-up as usual and column chromatography on silica gel elution with 100% EtOAc afforded the (5S)-5-[(N-benzoyl)amino]-4-oxo-6-phenyl-hexanoyl-L-tryptophan methyl ester as a yellow solid (0.290 g, 90%); mp 88-90° C.; Rf 0.50 (EtOAc); IR (KBr) ν 1760 (CO), 3230 (NH) cm−1; 1H NMR (300 MHz, CDCl3) δH 2.44 (2H, m, —CH2CO), 2.82 (2H, m, —CH2CO), 3.06 (1H, m, —CHαPh), 3.28 (3H, m, —CHβPh and —CH2Trp), 3.67 (3H, s, —OMe), 4.90 (1H, m, —CH—), 4.99 (1H, m, —CH—), 6.17 (1H, dd, J=2.7 and 7.5 Hz, —NH), 6.88 (1H, d, J=6.9 Hz, —NH), 7.00 (1H, dd, J=2.8 and 6.4 Hz, Trp-H-5′), 7.02-7.56 (12H, m, Ar—H), 7.68 (1H, d, J=1.8 Hz, Trp-H-2′), 7.71 (1H, d, J=1.8 Hz, Ar—H) and 8.27 (1H, br-s, —NH); 13C NMR (75 MHz, CDCl3) δC 27.6, 29.7, 35.0, 35.1, 36.8, 36.9, 52.3, 53.0, 59.4, 59.6, 109.9, 111.3, 118.5, 119.7, 122.2, 123.0, 127.0, 127.6 (2C), 128.5, 128.6 (2C), 129.3, 131.8, 133.8, 136.1, 136.2, 167.1, 171.1, 172.3 and 207.5; HRMS m/z calcd for C31H31N3O5 (M+) 525.22637, found 525.22637.

Workup

  1. washon silica gel elution with 100% EtOAc

Sources & evidence

ORD record
ord-7974c200108245f59bf49fa04710d96e
Source dataset
uspto-grants-2011_05
Patent number
US07951834B2

Reaction notes

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