Hydrochloric Acid → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(3-(2-(dimethylamino)ethyl)ureido)-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

HRID 85554

Reaction equation

[N:1]([C@:4]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]1[C@@H:6]1[C@@:19]([CH3:22])([CH2:20][CH2:21]2)[C@@:18]2([CH3:23])[C@@H:9]([C@:10]3([CH3:36])[C@@H:15]([CH2:16][CH2:17]2)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)=[CH:12][CH2:11]3)[CH2:8][CH2:7]1)=[C:2]=[O:3].C(N(CC)C(C)C)(C)C.[CH3:52][N:53]([CH3:57])[CH2:54][CH2:55][NH2:56].Cl>C1COCC1.CCOC(C)=O>[CH3:52][N:53]([CH3:57])[CH2:54][CH2:55][NH:56][C:2](=[O:3])[NH:1][C@:4]12[CH2:39][CH2:38][C@@H:37]([C:40]([CH3:42])=[CH2:41])[C@@H:5]1[C@@H:6]1[C@@:19]([CH3:22])([CH2:20][CH2:21]2)[C@@:18]2([CH3:23])[C@@H:9]([C@:10]3([CH3:36])[C@@H:15]([CH2:16][CH2:17]2)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]2[CH:35]=[CH:34][C:29]([C:30]([O:32][CH3:33])=[O:31])=[CH:28][CH:27]=2)=[CH:12][CH2:11]3)[CH2:8][CH2:7]1

Participants

Conditions

Temperature: 25 °C

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-isocyanato-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 (610.0 mg, 1.071 mmol) in THF (10 mL) was added N,N-diisopropylethylamine (0.559 mL, 3.21 mmol) and N,N-dimethylethylenediamine (0.353 mL, 3.21 mmol). The reaction mixture was stirred at 25° C. After 18 h, the reaction mixture was diluted with EtOAc (50 mL) and treated with 1N HCl (5 mL). The mixture was concentrated to a paste and then triturated with EtOAc, filtered and washed with Et2O. The white solid was saved and the liquid filtrate was concentrated and the trituration and filtration steps were repeated twice more. The combined white solid product was dried in a vacuum oven to give the title compound (650.0 mg, 0.958 mmol, 90% yield). LCMS: m/e 658.4 (M+H)+, 4.25 min (method 8). 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 7.9 (2H, d, J=8.5 Hz), 7.2 (2H, d, J=8.2 Hz), 5.3 (1H, dd, J=6.3, 1.7 Hz), 4.8 (1H, s), 4.6 (1H, s), 3.9 (3H, s), 3.7-3.8 (1H, m), 3.5-3.6 (1H, m), 3.2 (2H, br. s.), 2.9 (6H, br. s.), 2.7-2.7 (1H, m), 2.6 (1H, d, J=13.4 Hz), 2.4 (1H, dd, J=11.6, 8.2 Hz), 2.1 (1H, dd, J=17.2, 6.3 Hz), 2.0-2.1 (1H, m), 1.8-1.9 (1H, m), 1.8 (1H, d, J=12.8 Hz), 1.7 (3H, s), 1.7 (1H, d, J=6.7 Hz), 1.6-1.7 (1H, m), 1.5-1.6 (2H, m), 1.5 (4H, d, J=2.7 Hz), 1.3-1.4 (5H, m), 1.2-1.3 (1H, m), 1.1 (3H, s), 1.0-1.1 (2H, m), 1.0 (3H, s), 1.0-1.0 (3H, m), 0.9 (6H, s). 13C NMR (CHLOROFORM-d) δ ppm 14.2, 15.8, 16.3, 18.4, 19.2, 19.5, 20.7, 21.1, 25.0, 27.1, 29.1, 29.5, 29.6, 33.3, 35.3, 35.4, 36.0, 37.2, 37.3, 40.3, 41.4, 41.7, 43.4, 46.7, 49.3, 51.7, 52.6, 53.4, 58.9, 63.9, 77.3, 109.8, 123.9, 127.6, 128.2, 129.8, 145.9, 148.5, 149.4, 157.5, 167.0.

Workup

concentrationThe mixture was concentrated to a paste
customtriturated with EtOAc
filtrationfiltered
washwashed with Et2O
concentrationthe liquid filtrate was concentrated
filtrationthe trituration and filtration steps
customThe combined white solid product was dried in a vacuum oven

Sources & evidence

ORD record: ord-c0ea8c4d761c423b817aea1602c234ae
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846647B2

Linked notes

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