L-Tryptophan, methyl ester → HCID 57956918, compound

HRID 553075Notes

Reaction equation

HRID 553075 reaction equation
[CH2:1]([O:8][C:9](=[O:37])[C@@H:10]1[CH2:14][CH2:13][CH2:12][N:11]1[C:15](=[O:36])[CH2:16][CH2:17][C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:20][C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)C1C=CC=CC=1.C1(C[C@H](NC(OC(C)(C)C)=O)C(=O)CCC(O)=O)C=CC=CC=1.COC(=O)[C@H](CC1[C:75]2[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=2)[NH:69]C=1)N.O.ON1C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C>CN(C=O)C.C(Cl)Cl>[CH3:1][O:8][C:9](=[O:37])[C@H:10]([CH2:14][C:13]1[C:75]2[C:70](=[CH:71][CH:72]=[CH:73][CH:74]=2)[NH:69][CH:12]=1)[NH:11][C:15](=[O:36])[CH2:16][CH2:17][C:18](=[O:35])[C@@H:19]([NH:27][C:28]([O:30][C:31]([CH3:32])([CH3:34])[CH3:33])=[O:29])[CH2:20][C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Participants

7

Reactant 5

HCID 77980L-Tryptophan, methyl esterHCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 15109748HCID 15109748, compoundHCID 57956925HCID 57956925, compound

Product 1

HCID 57956918HCID 57956918, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The experimental procedure employed for the synthesis of (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-proline benzyl ester was followed using the free acid compound 9 (98 mg, 0.3054 mmol, 1.0 eq.), L-tryptophan methyl ester (67 mg, 0.3054 mmol, 1.0 eq.), 1-Hydroxybenzotriazole hydrate (HOBt) (42 mg, 0.3054 mmol, 1.0 eq.), N-ethyl-IV-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl) (59 mg, 0.3054 mmol, 1.0 eq.), iPr2NEt (0.055 mL, 0.3054 mmol, 1.0 eq.) and dry DMF/CH2Cl2 (2:8 ratio)(5 mL). Work-up as usual and column chromatography on silica gel elution with 50% EtOAc-hexane afforded the (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-tryptophan methyl ester (NACE 118) as a cream white solid (0.129 g, 81%): mp 54-57° C.; Rf 0.34 (50% EtOAc-hexane); IR (KBr) ν 1680 (CO) and 3000 (broad, NH) cm−1; 1H NMR (400 MHz, CDCl3) δH 1.40 (9H, s, (CH3)3), 2.41 (2H, t, J=6.6 Hz, —CH2CO), 2.74 (2H, m, —CH2CO), 2.88 (1H, m, —CHαPh), 3.10 (1H, m, —CHβPh), 3.30 (2H, m, —CH2Trp), 3.68 (3H, s, OCH3), 4.47 (1H, br s, —NH), 4.89 (1H, dd, J=5.5 and 11.0 Hz, —CH—), 5.03 (1H, m, —CH—), 6.07 (1H, d, J=7.3 Hz, —NH), 7.08-7.58 (10H, m, Ar—H) and 8.15 (1H, br s, —NH-indole); 13C NMR (100 MHz, CDCl3) δC 27.5, 28.3, 30.8, 35.4, 37.5, 52.3, 52.9, 53.0, 60.1, 111.2, 118.5, 119.7, 122.2, 122.9, 123.0, 126.9, 127.7, 128.6, 129.2, 129.3, 136.1, 136.3, 136.4, 155.4, 172.2, 172.3 and 204.6; EI-MS m/z calcd for C29H35N3O6 (M+) 521.2526, found 521 (M+).

Workup

  1. washon silica gel elution with 50% EtOAc-hexane

Sources & evidence

ORD record
ord-dedecf84d582458b8afec5f4e3a7a600
Source dataset
uspto-grants-2011_05
Patent number
US07951834B2

Reaction notes

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