(3bS,4aR)-5,5-Difluoro-3b,4,4a,5-tetrahydro-3-(trifluoromethyl)-1H-cyclopropa(3,4)cyclopenta(1,2-c)pyrazole-1-acetic acid → N-((S)-1-(5-amino-6-chloro-3-(4-chloro-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 2170391Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[C:4]([C:27]2[CH:28]=[CH:29][C:30]([Cl:42])=[C:31]3[C:35]=2[N:34]([CH3:36])[N:33]=[C:32]3[NH:37][S:38]([CH3:41])(=[O:40])=[O:39])[C:5]([C@@H:9]([NH:19][C:20](=[O:26])OC(C)(C)C)[CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)=[N:6][C:7]=1[Cl:8].[F:43][C:44]1([F:61])[C:48]2[N:49]([CH2:56]C(O)=O)[N:50]=[C:51]([C:52]([F:55])([F:54])[F:53])[C:47]=2[C@H:46]2[CH2:60][C@@H:45]12.FC(F)C1C2[C@H]3C[C@H]3C(F)(F)C=2N(CC(O)=O)N=1>>[NH2:1][C:2]1[CH:3]=[C:4]([C:27]2[CH:28]=[CH:29][C:30]([Cl:42])=[C:31]3[C:35]=2[N:34]([CH3:36])[N:33]=[C:32]3[NH:37][S:38]([CH3:41])(=[O:39])=[O:40])[C:5]([C@@H:9]([NH:19][C:20](=[O:26])[CH2:56][N:49]2[C:48]3[C:44]([F:43])([F:61])[C@@H:45]4[CH2:60][C@@H:46]4[C:47]=3[C:51]([C:52]([F:53])([F:54])[F:55])=[N:50]2)[CH2:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([F:18])[CH:12]=2)=[N:6][C:7]=1[Cl:8]

Participants

Reactant 3

HCID 90281286(3bS,4aR)-5,5-Difluoro-3b,4,4a,5-tetrahydro-3-(trifluoromethyl)-1H-cyclopropa(3,4)cyclopenta(1,2-c)pyrazole-1-acetic acid

HCID 902812892-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid

HCID 90290154(S)-tert-butyl (1-(5-amino-6-chloro-3-(4-chloro-1-methyl-3-(methylsulfonamido)-1H-indazol-7-yl)pyridin-2-yl)-2-(3,5-difluorophenyl)ethyl)carbamate

Product 1

HCID 90281233N-((S)-1-(5-amino-6-chloro-3-(4-chloro-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 54 was prepared from compound 53A according to the method presented for the synthesis of Example 49 substituting 2-((3bS,4aR)-5,5-difluoro-3-(trifluoromethyl)-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid for 2-((3bS,4aR)-3-(difluoromethyl)-5,5-difluoro-3b,4,4a,5-tetrahydro-1H-cyclopropa[3,4]cyclopenta[1,2-c]pyrazol-1-yl)acetic acid to provide 13 mg of title compound: 1H NMR (400 MHz, Methanol-d4) δ 7.12-6.94 (m, 2H), 6.81-6.60 (m, 1H), 6.55-6.35 (m, 2H), 6.25 (d, 1H), 5.01-4.90 (m, 1H), 4.76 (t, 2H), 3.41 (s, 2H), 3.24 (d, 3H), 3.15-2.88 (m, 3H), 2.48 (q, 2H), 1.47-1.38 (m, 1H), 1.16-1.04 (m, 1H). MS (m/z) 805 [M+H]+.

Sources & evidence

ORD record: ord-eaac06b06e554c56b93346ce61a7df9b
Source dataset: uspto-grants-2015_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09050344B2

Reaction notes

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