HCID 78321327, compound → HCID 78320689, compound

HRID 1773041Notes

Reaction equation

C(OC(NC1(C(O)=O)CC1/C=C/C1C(C)(C)[C@H]2[C@](C)(CC=1)[C@@H]1[C@](C)([C@@]3(C)[C@H](CC1)[C@H]1[C@H](C(C)=C)CC[C@]1(NCCN1CCS(=O)(=O)CC1)CC3)CC2)=O)(C)(C)C.[F:57][C:58]1([C:107]([O:109]CC)=[O:108])[CH2:63][CH2:62][C:61](=[CH:64][C:65]2[C:66]([CH3:106])([CH3:105])[C@H:67]3[C@:80]([CH3:83])([CH2:81][CH:82]=2)[C@@H:79]2[C@:70]([CH3:104])([C@@:71]4([CH3:103])[C@H:76]([CH2:77][CH2:78]2)[C@H:75]2[C@H:84]([C:87]([CH3:89])=[CH2:88])[CH2:85][CH2:86][C@:74]2([NH:90][CH2:91][CH2:92][N:93]2[CH2:98][CH2:97][CH:96]([S:99]([CH3:102])(=[O:101])=[O:100])[CH2:95][CH2:94]2)[CH2:73][CH2:72]4)[CH2:69][CH2:68]3)[CH2:60][CH2:59]1>>[F:57][C:58]1([C:107]([OH:109])=[O:108])[CH2:59][CH2:60][C:61](=[CH:64][C:65]2[C:66]([CH3:106])([CH3:105])[C@H:67]3[C@:80]([CH3:83])([CH2:81][CH:82]=2)[C@@H:79]2[C@:70]([CH3:104])([C@@:71]4([CH3:103])[C@H:76]([CH2:77][CH2:78]2)[C@H:75]2[C@H:84]([C:87]([CH3:89])=[CH2:88])[CH2:85][CH2:86][C@:74]2([NH:90][CH2:91][CH2:92][N:93]2[CH2:94][CH2:95][CH:96]([S:99]([CH3:102])(=[O:100])=[O:101])[CH2:97][CH2:98]2)[CH2:73][CH2:72]4)[CH2:69][CH2:68]3)[CH2:62][CH2:63]1

Participants

Reactant 2

HCID 78321327HCID 78321327, compound

HCID 86731499HCID 86731499, compound

Product 1

HCID 78320689HCID 78320689, compound

Procedure

1-fluoro-4-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperidin-1-yl)ethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)methylene)cyclohexanecarboxylic acid was prepared following the method described above for the preparation of 1-((tert-butoxycarbonyl)amino)-2-((E)-2-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(1,1-dioxidothiomorpholino)ethyl)amino)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)vinyl)cyclopropanecarboxylic acid, using ethyl 1-fluoro-4-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperidin-1-yl)ethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)methylene)cyclohexanecarboxylate as the reactant in step 2. The reaction crude was purified by prep HPLC (method 4) to afford the title compound as a mixture of isomers in 20.7% of yield. MS: m/e 755.5 (M+H)+, 2.610 min (method 4). 1H NMR (400 MHz, METHANOL-d4) δ 5.95-5.35 (m, 1H), 5.32-5.12 (m, 1H), 4.79 (br. s., 1H), 4.71 (s, 1H), 3.25-3.04 (m, 5H), 2.96 (s, 3H), 2.90-1.81 (m, 24H), 1.76 (s, 3H), 1.73-1.27 (m, 15H), 1.22 (br. s., 3H), 1.13-1.08 (m, 3H), 1.07-0.91 (m, 6H), 0.90-0.83 (m, 3H); 19F NMR (376 MHz, METHANOL-d4) δ −154.27-167.89 (m, 1F).

Workup

custom1-fluoro-4-(((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-(4-(methylsulfonyl)piperidin-1-yl)ethyl)amino)-1-(prop-1-en-2-yl)-2,3,3a,4,5,5a,5b,6,7,7a,8,11,11a,11b,12,13,13a,13b-octadecahydro-1H-cyclopenta[a]chrysen-9-yl)methylene)cyclohexanecarboxylic acid was prepared
customThe reaction crude
customwas purified by prep HPLC (method 4)

Sources & evidence

ORD record: ord-786101e12af146c38eb8015d4b39ee31
Source dataset: uspto-grants-2016_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09249180B2

Reaction notes

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