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

HRID 405077Notes

Reaction equation

HRID 405077 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[C:12]1[C:13]([CH3:42])([CH3:41])[C@H:14]2[C@:27]([CH3:30])([CH2:28][CH:29]=1)[C@@H:26]1[C@:17]([CH3:40])([C@@:18]3([CH3:39])[C@H:23]([CH2:24][CH2:25]1)[C@H:22]1[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]1([CH:37]=O)[CH2:20][CH2:19]3)[CH2:16][CH2:15]2)[C:5]([O:7]C)=[O:6].[NH2:43][CH2:44][CH2:45][CH2:46][N:47]1[CH2:51][CH2:50][CH2:49][C:48]1=[O:52]>>[F:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[C:12]1[C:13]([CH3:42])([CH3:41])[C@H:14]2[C@:27]([CH3:30])([CH2:28][CH:29]=1)[C@@H:26]1[C@:17]([CH3:40])([C@@:18]3([CH3:39])[C@H:23]([CH2:24][CH2:25]1)[C@H:22]1[C@H:31]([C:34]([CH3:36])=[CH2:35])[CH2:32][CH2:33][C@:21]1([CH2:37][NH:43][CH2:44][CH2:45][CH2:46][N:47]1[CH2:51][CH2:50][CH2:49][C:48]1=[O:52])[CH2:20][CH2:19]3)[CH2:16][CH2:15]2)[C:5]([OH:7])=[O:6]

Participants

3

Reactant 2

HCID 821111-(3-Aminopropyl)-2-pyrrolidinoneHCID 86676412methyl 3-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 715966174-[(1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-1-isopropenyl-5a,5b,8,8,11a-pentamethyl-3a-[[3-(2-oxopyrrolidin-1-yl)propylamino]methyl]-1,2,3,4,5,6,7,7a,11,11b,12,13,13a,13b-tetradecahydrocyclopenta[a]chrysen-9-yl]-3-fluoro-benzoic acidYield 79%

Procedure

The title compound was prepared in 79% yield following steps 5 and 6 described above, using methyl 3-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-(3-aminopropyl)pyrrolidin-2-one as the reactant amine MS: m/e 687.5 (MH+), 1.71 min (method 2). 1H NMR (400 MHz, MeOD) δ ppm 0.91 (s, 3H) 0.96 (s, 3H) 1.05 (s, 3H) 1.08 (s, 3H) 1.17 (s, 3H) 1.73 (s, 3H) 0.85-1.91 (m, 20H) 1.96-2.20 (m, 6H) 2.44 (t, J=8.03 Hz, 2H) 2.47-2.56 (m, 1H) 2.83 (d, J=13.05 Hz, 1H) 3.07 (t, J=7.03 Hz, 2H) 3.21 (d, J=13.05 Hz, 1H) 3.43 (t, J=6.40 Hz, 2H) 3.52 (t, J=7.15 Hz, 2H) 4.62-4.66 (m, 1H) 4.75 (d, J=1.51 Hz, 1H) 5.35 (dd, J=6.02, 1.51 Hz, 1H) 7.22 (t, J=7.65 Hz, 1H) 7.64 (dd, J=9.79, 1.51 Hz, 1H) 7.75 (dd, J=7.91, 1.63 Hz, 1H). 19F NMR (376 MHz, MeOD) δ ppm −114.92 (s, 1 F).

Workup

  1. customm/e 687.5 (MH+), 1.71 min (method 2)

Sources & evidence

ORD record
ord-fcde45bbbc3f4ee39efbde977dbabd26
Source dataset
uspto-grants-2014_06
Patent number
US08748415B2

Reaction notes

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