1-(2-Aminoethyl)pyrrolidin-2-one oxalate → 4-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-3a-[[2-(2-oxopyrrolidin-1-yl)ethylamino]methyl]-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]-2-fluoro-benzoic acid

HRID 405081Notes

Reaction equation

[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:13]([CH3:42])([CH3:41])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:40])([C@@:18]4([CH3:39])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([CH:37]=O)[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:9]=[CH:8][C:3]=1[C:4]([O:6]C)=[O:5].C(O)(=O)C(O)=O.[NH2:49][CH2:50][CH2:51][N:52]1[CH2:56][CH2:55][CH2:54][C:53]1=[O:57]>>[F:1][C:2]1[CH:11]=[C:10]([C:12]2[C:13]([CH3:42])([CH3:41])[C@H:14]3[C@:27]([CH3:30])([CH2:28][CH:29]=2)[C@@H:26]2[C@:17]([CH3:40])([C@@:18]4([CH3:39])[C@H:23]([CH2:24][CH2:25]2)[C@H:22]2[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]2([CH2:37][NH:49][CH2:50][CH2:51][N:52]2[CH2:56][CH2:55][CH2:54][C:53]2=[O:57])[CH2:20][CH2:19]4)[CH2:16][CH2:15]3)[CH:9]=[CH:8][C:3]=1[C:4]([OH:6])=[O:5]

Participants

Reactant 2

HCID 682759661-(2-Aminoethyl)pyrrolidin-2-one oxalate

HCID 86676413methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-formyl-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

Product 1

HCID 715973694-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-3a-[[2-(2-oxopyrrolidin-1-yl)ethylamino]methyl]-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]-2-fluoro-benzoic acidYield 60%

Procedure

The title compound was prepared in 60% yield following steps 5 and 6, using methyl 2-fluoro-4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-formyl-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 and 1-(2-aminoethyl)pyrrolidin-2-one oxalate as the reactant amine MS: m/e 673.6 (MH+), 1.72 min (method 2). 1H NMR (400 MHz, MeOD) δ ppm 0.96 (s, 3H) 0.98 (s, 3H) 1.02 (s, 3H) 1.08 (s, 3H) 1.17 (s, 3H) 1.73 (s, 3H) 2.01-2.21 (m, 4H) 2.44 (t, J=8.16 Hz, 2H) 2.51 (td, J=10.79, 5.52 Hz, 1H) 2.94 (d, J=13.05 Hz, 1H) 3.30 (dt, J=3.26, 1.63 Hz, 3H) 3.55 (t, J=7.15 Hz, 2H) 3.58-3.70 (m, 2H) 4.62-4.67 (m, 1H) 4.76 (d, J=1.76 Hz, 1H) 5.35 (dd, J=6.27, 1.76 Hz, 1H) 6.94 (dd, J=11.92, 1.38 Hz, 1H) 7.02 (dd, J=8.03, 1.51 Hz, 1H) 7.83 (t, J=7.91 Hz, 1H). 19F NMR (376 MHz, MeOD) δ ppm −112.75 (s, 1 F).

Workup

customm/e 673.6 (MH+), 1.72 min (method 2)

Sources & evidence

ORD record: ord-42bdfb59d4fb4e2181465f51f4691be1
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748415B2

Reaction notes

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