Trifluoroacetic acid → 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester

HRID 613869Notes

Reaction equation

HRID 613869 reaction equation
C([O:8]C(=O)CC(N1C=CC(C2C=CC=CC=2)=C1)C(NC1CC2=CN(C3C2=CC=CC=3)CCOCCNC1=O)=O)C1C=CC=CC=1.FC(F)(F)C(O)=O.[CH2:53]([O:56][C:57](=[O:73])[CH2:58][C@@H:59]([NH2:72])[C:60]([NH:62][C@H:63]([C:68](=[O:71])[NH:69][CH3:70])[C:64]([CH3:67])([CH3:66])[CH3:65])=[O:61])[CH:54]=[CH2:55].[C:74]([C:76]1[CH:81]=[CH:80][C:79]([C:82]#[C:83][CH:84]2[CH2:88][CH:87](OC)O[CH:85]2OC)=[CH:78][CH:77]=1)#[N:75].FC(F)(F)C(O)=O>CCCCCCC.CC(O)=O>[CH2:53]([O:56][C:57](=[O:73])[CH2:58][C@@H:59]([N:72]1[CH:87]=[CH:88][C:84]([C:83](=[O:8])[CH2:82][C:79]2[CH:80]=[CH:81][C:76]([C:74]#[N:75])=[CH:77][CH:78]=2)=[CH:85]1)[C:60]([NH:62][C@H:63]([C:68](=[O:71])[NH:69][CH3:70])[C:64]([CH3:65])([CH3:66])[CH3:67])=[O:61])[CH:54]=[CH2:55]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 18341503N-(8-oxo-4-oxa-1,7-diaza-tricyclo-[9.6.1.012,17]-octadeca-11(18), 12,14,16-tetraen-9-yl)-3-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl esterHCID 183803483-[2-(4-Cyanophenyl)-ethynyl]-2,5-dimethoxy-tetrahydrofuranHCID 865844093(R)-arnino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl ester trifluoroacetate salt

Product 1

HCID 700987653(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 8900HeptaneSolvent

Procedure

As described in Example 1(c) for the preparation of N-(8-oxo-4-oxa-1,7-diaza-tricyclo[9.6.1.012,17 ]octadeca-11(18),12,14,16-tetraen-9-yl)-3-(3-phenyl-1H-pyrrol-1-yl)succinamic acid benzyl ester, 3(R)-amino-N-(2,2-dimethyl-1(S)-(methylcarbamoyl)propyl)succinamic acid allyl ester trifluoroacetate salt and 3-[2-(4-cyanophenyl)-ethynyl]-2,5-dimethoxy-tetrahydrofuran were heated with trifluoroacetic acid (1 equiv) at 70° C. for 4 hours. Flash column chromatography twice with 0.5% HOAc/15% EtOAc/CH2Cl2 as eluant and azeotrope with n-heptane afforded 800 mg (36%, 43% based on recovered furan) of 3(R)-[3-[(4-cyanophenyl)acetyl]-1H-pyrrol-1-yl]-N-[2,2-dimethyl-1(S)-(methylcarbamoyl)propyl]succinamic acid allyl ester as a brown oil. 1H NMR (CDCl3): δ 7.58 (d, 2H, J=8.1 Hz), 7.47 (dd, 1H, J=1.9, 1.9 Hz), 7.36 (d, 2H, J=8.1 Hz), 6.84 (d, 1H, J=9.0 Hz), 6.74 (dd, 1H, J=2.8, 2.8 Hz), 6.63 (dd, 1H, J=1.6, 2.8 Hz), 6.08 (dd, J=2.8, 6.8 Hz), 5.82 (ddt, 1H, J=5.9, 10.3, 17.1 Hz), 5.26 (ddd, 1H, J=1.2, 2.8, 17.1 Hz), 5.19 (q, 1H, J=7.2 Hz), 4.56 (dddd, 2H, J=1.6, 2.8, 4.4, 15.9 Hz), 4.18 (d, 1H, J=9.0 Hz), 4.05 (s, 2H), 3.34 (dd, 1H, J=7.2, 16.8 Hz), 2.99 (dd, 1H, J=7.2, 16.8 Hz), 2.72 (d, 3H, J=5.0 Hz), 0.90 (s, 9H). 13C NMR (CDCl3): δ 191.2, 170.2, 169.4, 168.0, 140.6, 132.2, 131.3, 130.3, 125.7, 125.7, 122.0, 119.0, 118.9, 110.5, 110.4, 66.0, 61.0, 59.4, 46.1, 37.5, 34.8, 31.9, 29.0, 26.5, 26.0. IR (KBr): 3320, 2965, 229, 1736, 1648, 1531, 1173 cm-1. HRFABMS: Calculated for C27H33N4O5 (M+H+): 493.2451. Found 493.2462. Anal. Calculated for C27H32N4O5.0.2 H2O.0.2 CH2Cl2 : C, 63.66; H, 6.44; N, 10.92. Found: C, 63.86; H, 6.56; N, 10.58.

Sources & evidence

ORD record
ord-15184027b9744527bfa02b9d4ddba866
Source dataset
uspto-grants-1999_12
Patent number
US06008243

Reaction notes

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