Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate → N-(2,2-dimethyl-1(S)-(N-methylcarbamoyl)-propyl)-2-(2-biphenyl-4-yl-furan-5-yl)-acetamide

HRID 613931Notes

Reaction equation

HRID 613931 reaction equation
C(OC(=O)C(N)[C@@H](C(OC(C)(C)C)=O)C(N[C@@H](CC1C=CC=CC=1)COC)=O)C1C=CC=CC=1.[C:35]1([C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=2)[CH:40]=[CH:39][C:38]([C:41]2[O:42][C:43]([CH2:46][C:47]([OH:49])=O)=[CH:44][CH:45]=2)=[CH:37][CH:36]=1.FC(F)(F)C(O)=O.[CH3:63][NH:64][C:65](=[O:72])[C@H:66]([C:68]([CH3:71])([CH3:70])[CH3:69])[NH2:67].F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>CO.C(Cl)Cl>[CH3:69][C:68]([CH3:71])([CH3:70])[C@H:66]([NH:67][C:47](=[O:49])[CH2:46][C:43]1[O:42][C:41]([C:38]2[CH:37]=[CH:36][C:35]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)=[CH:40][CH:39]=2)=[CH:45][CH:44]=1)[C:65](=[O:72])[NH:64][CH3:63]

Participants

6

Reactant 4

HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 18341348l-t-Leucine-n-methylamide trifluoroacetate saltHCID 183803012-(2-Biphenyl-4-yl-furan-5-yl)-acetic acidHCID 70080702N-(1(S)-benzyl-2-methoxy-ethyl)-3(R)-t-butoxycarbonyl-amino-succinamic acid benzyl ester

Product 1

HCID 18341365N-(2,2-dimethyl-1(S)-(N-methylcarbamoyl)-propyl)-2-(2-biphenyl-4-yl-furan-5-yl)-acetamideYield 58%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

According to the procedure described in Example 1(f) for the preparation of N-(1(S)-benzyl-2-methoxy-ethyl)-3(R)-t-butoxycarbonyl-amino-succinamic acid benzyl ester, 2-(2-biphenyl-4-yl-furan-5-yl)-acetic acid was coupled to L-t-leucine N-methylamide trifluoroacetic acid salt with BOP. Flash column chromatography with 0-5% MeOH/CH2Cl2 gradient eluant provided in 58% yield N-[2,2-dimethyl-1(S)-(N-methyl-carbamoyl)-propyl]-2-(2-biphenyl-4-yl-furan-5-yl)-acetamide as an orange foam, which decomposed >75° C. and was used without further purification. 1H NMR (acetone-d6): δ 7.72 (d, 2H, J=8.5 Hz), 7.61 (d, 4H, J=7.7 Hz), 7.45 (t, 2H, J=7.5 Hz), 7.35 (t, 1H, J=7.4 Hz), 6.65 (d, 1H, J=3.3 Hz), 6.56 (d, 1H, J=9.2 Hz), 6.36 (d, 1H, J=3.3 Hz), 5.93 (bs, 1H), 4.22 (d, 1H, J=9.2 Hz), 3.71 (s, 2H), 2.79 (d, 3H, J=4.5 Hz), 0.94 (s, 9H). Anal. Calculated for C25H28N2O3.0.6 H2O.0.1 MTBE: C, 72.21; H, 7.23; N, 6.61. Found: C, 72.10; H, 6.97; N, 6.39.

Sources & evidence

ORD record
ord-adc6f96d880e4994a844cf7af020b1e0
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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