4-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid → 2-(4-(N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)phenyl)acetic acid

HRID 528919Notes

Reaction equation

ClC1C(C(=O)N(CCCC)CCCC)=NN(C2C=CC(C(O)=O)=CC=2C(N2CCC3C(=CC=CC=3)C2)=O)C=1C.[CH2:40]([N:44]([C:88]1[CH:93]=[CH:92][C:91]([CH2:94][C:95]([O:97]CC)=[O:96])=[CH:90][CH:89]=1)[C:45]([C:47]1[C:51]([Cl:52])=[C:50]([CH3:53])[N:49]([C:54]2[CH:59]=[CH:58][C:57]([C:60](=[O:75])[NH:61][S:62]([C:65]3[CH:74]=[CH:73][C:72]4[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=4)[CH:66]=3)(=[O:64])=[O:63])=[CH:56][C:55]=2[C:76]([N:78]2[CH2:87][CH2:86][C:85]3[C:80](=[CH:81][CH:82]=[CH:83][CH:84]=3)[CH2:79]2)=[O:77])[N:48]=1)=[O:46])[CH2:41][CH2:42][CH3:43]>>[CH2:40]([N:44]([C:88]1[CH:89]=[CH:90][C:91]([CH2:94][C:95]([OH:97])=[O:96])=[CH:92][CH:93]=1)[C:45]([C:47]1[C:51]([Cl:52])=[C:50]([CH3:53])[N:49]([C:54]2[CH:59]=[CH:58][C:57]([C:60](=[O:75])[NH:61][S:62]([C:65]3[CH:74]=[CH:73][C:72]4[C:67](=[CH:68][CH:69]=[CH:70][CH:71]=4)[CH:66]=3)(=[O:63])=[O:64])=[CH:56][C:55]=2[C:76]([N:78]2[CH2:87][CH2:86][C:85]3[C:80](=[CH:81][CH:82]=[CH:83][CH:84]=3)[CH2:79]2)=[O:77])[N:48]=1)=[O:46])[CH2:41][CH2:42][CH3:43]

Participants

Reactant 2

HCID 710621944-(4-Chloro-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid

HCID 71063123ethyl 2-(4-(N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)phenyl)acetate

Product 1

HCID 710630852-(4-(N-Butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)phenyl)acetic acidYield 53%

Procedure

Following a procedure analogous to that for the synthesis of Intermediate 1F, ethyl 2-(4-(N-butyl-4-chloro-5-methyl-1-(4-(naphthalen-2-ylsulfonylcarbamoyl)-2-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)phenyl)-1H-pyrazole-3-carboxamido)phenyl)acetate (Example 155, 1 mg, 9.9 μmol) was converted to the title compound (0.5 mg, 53%). 1H NMR (CD3OD, 2:1 mixture of amide rotamers) δ 8.71 (s, 1H), 8.10 (d, J=9.2 Hz, 1H), 8.06 (s, 2H), 8.03-7.97 (m, 2.5H), 7.94-7.91 (m, 0.5H), 7.73-7.65 (m, 2H), 7.41 (br s, 0.5H), 7.30 (br s, 0.5H), 7.23-7.10 (m, 5H), 7.03-6.96 (m, 1H), 6.90 (d, J=8.4 Hz, 1H), 6.61 (br s, 1H), 4.73 (br s, 1H), 4.48-4.19 (m, 2H), 4.07 (br s, 1H), 3.91 (br s, 1H), 3.54-3.39 (m, 2H), 2.95-2.75 (m, 2H), 2.10 (s, 2H), 2.01 (s, 1H), 1.65-1.55 (m, 1H), 1.40-1.18 (m, 5H), 0.92-0.80 (m, 3H); MS(ESI+) m/z 818.3 (M+H)+.

Sources & evidence

ORD record: ord-1adcbfb3234e4f02879558a3be23acd0
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346795B2

Reaction notes

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