Trifluoroacetic acid → (R)-5-[1-(3-Phenyl-allyl)-1H-indol-3-yl]-4-(7-phenyl-heptanoylamino)-pent-2-enoic acid methyl ester

HRID 852851Notes

Reaction equation

HRID 852851 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CCN(C(C)C)C(C)C.FC(F)(F)C(O)=O.[CH3:59][O:60][C:61](=[O:85])[CH:62]=[CH:63][CH:64]([NH2:84])[CH2:65][C:66]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[N:68]([CH2:75][CH:76]=[CH:77][C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[CH:67]=1>C1COCC1>[CH3:59][O:60][C:61](=[O:85])[CH:62]=[CH:63][C@H:64]([NH:84][C:13](=[O:15])[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[CH2:65][C:66]1[C:74]2[C:69](=[CH:70][CH:71]=[CH:72][CH:73]=2)[N:68]([CH2:75][CH:76]=[CH:77][C:78]2[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=2)[CH:67]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 81531Diisopropylethylamine2×HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 5209877-Phenyl heptanoic acidHCID 694139904-amino-5-[1-(3-phenyl-allyl)-1H-indol-3-yl]-pent-2-enoic acid methyl ester

Product 1

HCID 69417299(R)-5-[1-(3-Phenyl-allyl)-1H-indol-3-yl]-4-(7-phenyl-heptanoylamino)-pent-2-enoic acid methyl esterYield 57.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of 7-phenylheptanoic acid (87 mg, 0.422 mmol), BOP (205 mg, 0.464 mmol) and DIPEA (65.38 mg, 88 μL, 0.506 mmol) in THF (2.5 mL) was stirred for 10 min. To this was added a solution of the trifluoroacetic acid salt of 4-amino-5-[1-(3-phenyl-allyl)-1H-indol-3-yl]-pent-2-enoic acid methyl ester (200 mg, 0.422 mmol) and DIPEA (163 mg, 220 μL, 1.27 mmol) in THF (2.5 mL). The mixture was stirred overnight at room temperature. The solvent was removed and the crude material subject to column chromatography (50% EtOAc/petroleum ether, Rf 0.66) to afford the title compound (133 mg, 55%). 1H NMR (CDCl3) δ 7.58 (1H, d, J=8.1 Hz), 7.36-7.09 (12H, m), 7.02-6.95 (2H, m), 6.45 (1H, d, J=15.78 Hz), 6.29 (1H, dt, J=5.63, 15.78 Hz), 5.82 (1H, d, J=15.69 Hz), 5.52 (1H, d, J=8.25 Hz), 5.01-5.09 (1H, m), 4.82 (2H, d, J=5.49 Hz), 3.66 (3H, s), 3.12 (1H, dd, J=6.35, 14.69 Hz), 3.04 (1H, dd, J=6.17, 14.69 Hz), 2.55 (2H, t, J=7.69 Hz), 2.07 (2H, t, J=7.64 Hz), 1.59-1.46 (4H, m), 1.25-1.23 (4H, m). 13C NMR (CDCl3) δ 172.5, 166.6, 148.1, 142.7, 136.4, 136.1, 132.5, 128.6, 128.4, 128.2, 127.9, 126.5, 125.6, 124.6, 120.8, 122.0, 119.5, 118.8, 109.8, 109.2, 51.6, 50.2, 48.3, 36.7, 35.8, 31.2, 29.9, 29.0, 28.9, 25.4. ISMS: 549 (M+H).

Workup

  1. customThe solvent was removed

Sources & evidence

ORD record
ord-93a8119c7c0e4850adf494c5066c36e2
Source dataset
uspto-grants-2007_08
Patent number
US07253194B2

Reaction notes

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