Lithium Hydroxide → 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(2-(1-methyl-1H-imidazol-2-ylamino)ethylamino)-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

HRID 85680

Reaction equation

HRID 85680 reaction equation
[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:22])([CH3:21])[C:14]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:5]1([NH:39][CH2:40][CH2:41][NH:42][C:43]1C=NC=CC=1)[CH2:4][CH2:3]2.Br[C:50]1[N:51](C)[CH:52]=[CH:53][N:54]=1.[Li+].[OH-].C(O)(C(F)(F)F)=O>CO.O>[CH3:1][C@:2]12[C@@:19]3([CH3:20])[C@@H:10]([C@:11]4([CH3:32])[C@@H:16]([CH2:17][CH2:18]3)[C:15]([CH3:21])([CH3:22])[C:14]([C:23]3[CH:31]=[CH:30][C:26]([C:27]([OH:29])=[O:28])=[CH:25][CH:24]=3)=[CH:13][CH2:12]4)[CH2:9][CH2:8][C@@H:7]1[C@H:6]1[C@H:33]([C:36]([CH3:38])=[CH2:37])[CH2:34][CH2:35][C@:5]1([NH:39][CH2:40][CH2:41][NH:42][C:43]1[N:51]([CH3:50])[CH:52]=[CH:53][N:54]=1)[CH2:4][CH2:3]2

Participants

7

Reactant 4

HCID 3939Lithium HydroxideHCID 6422Trifluoroacetic acidHCID 27732622-Bromo-1-methyl-1H-imidazoleHCID 683582194-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(2-(pyridin-3-ylamino)ethylamino)-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 683581134-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-(2-(1-methyl-1H-imidazol-2-ylamino)ethylamino)-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

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The title compound was prepared following a similar procedure as described for the synthesis of 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(2-(pyridin-3-ylamino)ethylamino)-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 2-bromo-1-methyl-1H-imidazole (0.015 g, 8.88 μL, 0.091 mmol) was used in place of 3-bromopyridine. Also, addition of LiOH, water and methanol were unnecessary for this example, as the ester hydrolysis occurred spontaneously during the course of the amination reaction. The product was isolated after reverse phase preparative HPLC purification using Prep HPLC Method 8 as a beige solid (38.1 mg, 51.5% yield) bis TFA salt. LCMS: m/e 653.4 (M+H)+, 3.88 min (method 16). 1H NMR (500 MHz, 1:1 mixture of CDCl3 and MeOD, MeOD lock) δ ppm 7.91 (d, J=8.2 Hz, 2H), 7.19 (d, J=7.9 Hz, 2H), 6.86 (s, 1H), 6.83-6.79 (m, 1H), 5.28 (d, J=5.5 Hz, 1H), 4.84 (s, 1H), 4.73 (s, 1H), 4.71 (br. s., 1H), 3.98-3.82 (m, 2H), 3.58 (s, 3H), 3.25 (br. s., 1H), 2.89-2.78 (m, 1H), 2.18-2.07 (m, 3H), 2.05-1.92 (m, 3H), 1.90-1.79 (m, 1H), 1.72 (s, 4H), 1.69 (br. s., 1H), 1.62-1.54 (m, 3H), 1.53-1.47 (m, 3H), 1.46-1.34 (m, 5H), 1.28-1.20 (m, 2H), 1.18-1.12 (m, 1H), 1.11 (s, 3H), 1.09-1.03 (m, 4H), 1.01 (s, 3H), 0.93 (br. s., 3H), 0.93 (br. s., 3H).

Workup

  1. customoccurred spontaneously during the course of the amination reaction
  2. customThe product was isolated
  3. customafter reverse phase preparative HPLC purification

Sources & evidence

ORD record
ord-6cad7a1dcb04464688da14b1e661453a
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Linked notes

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