6-(BOC-amino)-3-azabicyclo[3.1.0]hexane → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-3a-[2-[6-(methanesulfonamido)-3-azabicyclo[3.1.0]hexan-3-yl]ethylamino]-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoic acid

HRID 338646Notes

Reaction equation

HRID 338646 reaction equation
N1([C@]23CC[C@@H](C(C)=C)[C@@H]2[C@@H]2[C@@](C)(CC3)[C@@]3(C)[C@@H]([C@]4(C)[C@@H](CC3)C(C)(C)C(C3C=CC(C(OC)=O)=CC=3)=CC4)CC2)CC1.[CH3:43][C@:44]12[C@@:61]3([CH3:62])[C@@H:52]([C@:53]4([CH3:74])[C@@H:58]([CH2:59][CH2:60]3)[C:57]([CH3:64])([CH3:63])[C:56]([C:65]3[CH:73]=[CH:72][C:68]([C:69]([OH:71])=[O:70])=[CH:67][CH:66]=3)=[CH:55][CH2:54]4)[CH2:51][CH2:50][C@@H:49]1[C@H:48]1[C@H:75]([C:78]([CH3:80])=[CH2:79])[CH2:76][CH2:77][C@:47]1([NH:81][CH2:82][CH2:83][N:84]1[CH2:89][C@@H:88]3[CH2:90][C@@H:86]([N:87]3[S:91]([CH3:94])(=[O:93])=[O:92])[CH2:85]1)[CH2:46][CH2:45]2.C12C(NC(=O)OC(C)(C)C)C1CNC2>>[CH3:43][C@:44]12[C@@:61]3([CH3:62])[C@@H:52]([C@:53]4([CH3:74])[C@@H:58]([CH2:59][CH2:60]3)[C:57]([CH3:63])([CH3:64])[C:56]([C:65]3[CH:73]=[CH:72][C:68]([C:69]([OH:71])=[O:70])=[CH:67][CH:66]=3)=[CH:55][CH2:54]4)[CH2:51][CH2:50][C@@H:49]1[C@H:48]1[C@H:75]([C:78]([CH3:80])=[CH2:79])[CH2:76][CH2:77][C@:47]1([NH:81][CH2:82][CH2:83][N:84]1[CH2:85][CH:86]3[CH:90]([CH:88]3[NH:87][S:91]([CH3:94])(=[O:93])=[O:92])[CH2:89]1)[CH2:46][CH2:45]2

Participants

4

Reactant 3

HCID 111483086-(BOC-amino)-3-azabicyclo[3.1.0]hexaneHCID 86701802methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-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)benzoateHCID 867018094-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-((1R,5S)-6-(methylsulfonyl)-3,6-diazabicyclo[3.1.1]heptan-3-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)benzoic acid

Product 1

HCID 722033194-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-3a-[2-[6-(methanesulfonamido)-3-azabicyclo[3.1.0]hexan-3-yl]ethylamino]-5a,5b,8,8,11a-pentamethyl-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]benzoic acidYield 12%

Procedure

4-((1R,3 aS,5aR,5bR,7aR,11 aS,11bR,13 aR,13bR)-5a,5b,8,8,11a-Pentamethyl-3a-((2-(6-(methylsulfonamido)-3-azabicyclo[3.1.0]hexan-3-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)benzoic acid was prepared in 12% yield over three steps from methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-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)benzoate following the method used in the preparation of 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-((1R,5S)-6-(methylsulfonyl)-3,6-diazabicyclo[3.1.1]heptan-3-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)benzoic acid; except in step 1 tert-butyl 3-azabicyclo[3.1.0]hexan-6-ylcarbamate was used instead of (1R,5S)-tert-butyl 3,6-diazabicyclo[3.1.1]heptane-6-carboxylate. LC/MS: m/e 732.5 (M+H)+, 3.86 min (method 8). 1H NMR (400 MHz, 1:1 CDCl3:METHANOL-d4) δ 7.90 (d, J=8.3 Hz, 2H), 7.18 (d, J=8.3 Hz, 2H), 5.28 (d, J=4.9 Hz, 1H), 5.23 (s, 1H), 5.13 (s, 1H), 4.85 (s, 1H), 4.72 (br. s., 1H), 3.85 (br. s., 2H), 3.72 (br. s., 2H), 3.48 (br. s., 4H), 3.09 (br. s., 1H), 3.03 (s, 3H), 2.81 (d, J=10.3 Hz, 1H), 2.25-1.97 (m, 8H), 1.87 (d, J=11.5 Hz, 1H), 1.79-1.60 (m, 6H), 1.53 (d, J=16.1 Hz, 6H), 1.44-1.33 (m, 4H), 1.30-1.23 (m, 2H), 1.21 (br. s., 3H), 1.11-1.04 (m, 3H), 1.02 (s, 3H), 0.94 (s, 3H), 0.93 (br. s., 3H).

Workup

  1. customm/e 732.5 (M+H)+, 3.86 min (method 8)

Sources & evidence

ORD record
ord-891ec95dba7045329713e269d3e81bc1
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

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