Benzyl 4-(3-(butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate → 4-(3-(Butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid

HRID 528938Notes

Reaction equation

BrC1C(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]([CH2:82][C:83]1[CH:88]=[CH:87][C:86]([Cl:89])=[C:85]([Cl:90])[CH:84]=1)[C:45]([C:47]1[C:51]([Cl:52])=[C:50]([CH3:53])[N:49]([C:54]2[CH:69]=[CH:68][C:57]([C:58]([O:60]CC3C=CC=CC=3)=[O:59])=[CH:56][C:55]=2[C:70]([N:72]2[CH2:81][CH2:80][C:79]3[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=3)[CH2:73]2)=[O:71])[N:48]=1)=[O:46])[CH2:41][CH2:42][CH3:43]>>[CH2:40]([N:44]([CH2:82][C:83]1[CH:88]=[CH:87][C:86]([Cl:89])=[C:85]([Cl:90])[CH:84]=1)[C:45]([C:47]1[C:51]([Cl:52])=[C:50]([CH3:53])[N:49]([C:54]2[CH:69]=[CH:68][C:57]([C:58]([OH:60])=[O:59])=[CH:56][C:55]=2[C:70]([N:72]2[CH2:81][CH2:80][C:79]3[C:74](=[CH:75][CH:76]=[CH:77][CH:78]=3)[CH2:73]2)=[O:71])[N:48]=1)=[O:46])[CH2:41][CH2:42][CH3:43]

Participants

Reactant 2

HCID 71062139Benzyl 4-(3-(butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate

HCID 710624584-(4-Bromo-3-(dibutylcarbamoyl)-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acid

Product 1

HCID 710621524-(3-(Butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoic acidYield 98.2%

Procedure

Following a procedure analogous to that for the synthesis of Intermediate 164B, benzyl 4-(3-(butyl(3,4-dichlorobenzyl)carbamoyl)-4-chloro-5-methyl-1H-pyrazol-1-yl)-3-(1,2,3,4-tetrahydroisoquinoline-2-carbonyl)benzoate (2.20 g, 2.96 mmol) was converted to the title compound (1.90 g, 98%). 1H NMR (DMSO-d6, mixture of amide rotamers) δ 8.15 (d, J=8.4 Hz, 1H), 8.05 (d, J=2.2 Hz, 0.5H), 8.01-7.96 (m, 0.5H), 7.88-7.69 (m, 1H), 7.60-7.48 (m, 1.5H), 7.46-7.38 (m, 0.5H), 7.35-7.26 (m, 1H), 7.24-6.94 (m, 3H), 6.85 (d, J=7.5 Hz, 0.5H), 6.45-6.31 (m, 0.5H), 5.13 (br s, 0.5H), 4.85-4.15 (m, 4H), 3.74-3.36 (m, 2H), 3.23-2.92 (m, 1.5H), 2.82-2.60 (m, 2H), 2.31-2.11 (m, 3H), 1.45-1.08 (m, 3H), 1.05-0.90 (m, 1H), 0.82 (quin, J=7.2 Hz, 2H), 0.71-0.54 (m, 1H); MS (ESI+) m/z 655.1 (M+H)+.

Sources & evidence

ORD record: ord-27f1e1aee6c9490da0f7dbe44b9a9e13
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346795B2

Reaction notes

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