N-((S)-1-(6-chloro-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide → N-((1S)-1-(6-(4-amino-2-oxopyrrolidin-1-yl)-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide

HRID 2170381Notes

Reaction equation

Br[C:2]1[C:3]([C@@H:14]([NH:24][C:25](=[O:31])OC(C)(C)C)CC2C=C(F)C=C(F)C=2)=[N:4]C(N2CC(O)(C)C2)=CC=1.Cl[C:33]1[N:38]=[C:37]([C@@H:39]([NH:49][C:50](=[O:67])[CH2:51][N:52]2[C:56]3[C:57]([F:62])([F:61])[C@@H:58]4[CH2:60][C@@H:59]4[C:55]=3[C:54]([C:63]([F:66])([F:65])[F:64])=[N:53]2)[CH2:40][C:41]2[CH:46]=[C:45]([F:47])[CH:44]=[C:43]([F:48])[CH:42]=2)[C:36]([C:68]2[CH:69]=[CH:70][CH:71]=[C:72]3[C:76]=2[N:75]([CH3:77])[N:74]=[C:73]3[NH:78][S:79]([CH3:82])(=[O:81])=[O:80])=[CH:35][CH:34]=1.BrC1C([C@@H](NC(=O)OC(C)(C)C)CC2C=C(F)C=C(F)C=2)=NC(Br)=CC=1>>[NH2:4][CH:3]1[CH2:14][N:24]([C:33]2[N:38]=[C:37]([C@@H:39]([NH:49][C:50](=[O:67])[CH2:51][N:52]3[C:56]4[C:57]([F:62])([F:61])[C@@H:58]5[CH2:60][C@@H:59]5[C:55]=4[C:54]([C:63]([F:66])([F:65])[F:64])=[N:53]3)[CH2:40][C:41]3[CH:46]=[C:45]([F:47])[CH:44]=[C:43]([F:48])[CH:42]=3)[C:36]([C:68]3[CH:69]=[CH:70][CH:71]=[C:72]4[C:76]=3[N:75]([CH3:77])[N:74]=[C:73]4[NH:78][S:79]([CH3:82])(=[O:81])=[O:80])=[CH:35][CH:34]=2)[C:25](=[O:31])[CH2:2]1

Participants

Reactant 3

HCID 90281204N-((S)-1-(6-chloro-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide

HCID 90290190tert-Butyl (S)-(1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

HCID 90290192(S)-tert-butyl (1-(3-bromo-6-(3-hydroxy-3-methylazetidin-1-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

Product 1

HCID 90290137N-((1S)-1-(6-(4-amino-2-oxopyrrolidin-1-yl)-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide

Procedure

Compound 43B was prepared according to the method presented in the synthesis of compound 42G of Example 42 substituting N—((S)-1-(6-chloro-3-(1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)-2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetamide (43A) for (S)-Atert-butyl (1-(3,6-dibromopyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate (42F). 1H NMR (400 MHz, methanol-d4) δ 8.69-8.34 (m, 2H), 7.91-7.67 (m, 2H), 7.38-6.89 (m, 1H), 6.93-6.52 (m, 1H), 6.48-6.14 (m, 2H), 5.39-4.92 (m, 1H), 4.84-4.70 (m, 2H), 4.69-4.33 (m, 2H), 4.27 (m, 1H), 3.48-2.72 (m, 10H), 2.62-2.28 (m, 2H), 1.61-1.27 (m, 1H), 1.08 (m, 1H). MS (m/z) 820.00[M+H]+.

Sources & evidence

ORD record: ord-af1cc4d16e22485c9efeecf915439732
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09050344B2

Reaction notes

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