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Trifluoroacetic acid → 3(R)-(3-biphenyl-4-yl-1H-pyrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl ester

HRID 2299934
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HRID 2299934 반응식
C(OC(=O)CC(N1C=CC(C2C=CC=CC=2)=C1)C(NC1CC2=CN(C3C2=CC=CC=3)CCOCCNC1=O)=O)C1C=CC=CC=1.[CH2:46]([O:53][C:54](=[O:72])[CH2:55][C@@H:56]([NH2:71])[C:57]([NH:59][C@H:60]([C:65](=[O:70])[N:66]([O:68][CH3:69])[CH3:67])[CH2:61][CH:62]([CH3:64])[CH3:63])=[O:58])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1.[C:73]1([C:88]2[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=2)[CH:78]=[CH:77][C:76]([CH:79]2[CH2:83][CH:82](OC)O[CH:80]2OC)=[CH:75][CH:74]=1.FC(F)(F)C(O)=O.C(OC(=O)[C@H](N1C=CC(C2C=CC(C3C=CC=CC=3)=CC=2)=C1)CC(N[C@H](C(=O)N(OC)C)CC(C)C)=O)C1C=CC=CC=1>ClCCCl>[CH2:46]([O:53][C:54](=[O:72])[CH2:55][C@@H:56]([N:71]1[CH:82]=[CH:83][C:79]([C:76]2[CH:77]=[CH:78][C:73]([C:88]3[CH:93]=[CH:92][CH:91]=[CH:90][CH:89]=3)=[CH:74][CH:75]=2)=[CH:80]1)[C:57]([NH:59][C@H:60]([C:65](=[O:70])[N:66]([O:68][CH3:69])[CH3:67])[CH2:61][CH:62]([CH3:63])[CH3:64])=[O:58])[C:47]1[CH:48]=[CH:49][CH:50]=[CH:51][CH:52]=1
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7

반응물 5

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 183803263-Biphenyl-4-yl-2,5-dimethoxytetrahydrofuranHCID 542082503(R)-amino-N-(1(S)-(N-methoxy-N-methylcarbamoyl)-3-methylbutyl)succinamic acid benzyl ester
HCID 86758714
(R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl ester

생성물 1

HCID 599245073(R)-(3-biphenyl-4-yl-1H-pyrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl ester수율 48%

시약·촉매·용매 1

HCID 111,2-Dichloroethane용매

실험 절차

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-(1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl)succinamic acid benzyl ester was deprotected. The crude amine salt and 3-biphenyl-4-yl-2,5-dimethoxy-tetrahydrofuran (prepared as described in Example 1(a)) were condensed in anhydrous 1,2-dichloroethane with trifluoroacetic acid to provide in 48% yield 3 (R)-(3-biphenyl-4-yl-1H-pyrrol-1-yl)-N-[1(S)-(N-methoxy-N-methylcarbamoyl)-3-methyl-butyl]succinamic acid benzyl ester as an amorphous solid. 1H NMR (CDCl3) δ 7.62 (d, 2H, J=7.4 Hz), 7.58 (s, 3H), 7.44 (t, 2H, J=7.7 Hz), 7.35-7.21 (m, 7H), 7.10 (s, 1H), 6.80 (t, 1H, J=2.2 Hz), 6.60 (bs, 1H), 5.17-1.13 (m, 1H), 5.10 (s, 2H), 4.97-4.92 (m, 1H), 3.77 (s, 3H), 3.44 (dd, 1H, J=5.7, 17.1 Hz), 3.17 (s, 3H), 3.03 (dd, 1H, J=8.8, 16.5 Hz), 1.67-1.36 (m, 3H), 0.92 (d, 3H, J=6.25 Hz), 0.87 (d, 3H, J=6.3 Hz). Anal. Calculated for C35H39N3O5: C, 72.27; H, 6.76; N, 7.22. Found: C, 72.19; H, 6.78; N, 7.16.

출처 및 근거

ORD 기록
ord-88c0dd15e8474cce9321c165e2000338
출처 데이터셋
uspto-grants-2002_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06495699B2

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