Hydrochloric Acid → HCID 86575414, compound

HRID 1401005Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:16][CH2:17][NH:18][C@:19]23[CH2:63][CH2:62][C@@H:61]([C:64]([CH3:66])=[CH2:65])[C@@H:20]2[C@@H:21]2[C@@:34]([CH3:37])([CH2:35][CH2:36]3)[C@@:33]3([CH3:38])[C@@H:24]([C@:25]4([CH3:60])[C@@H:30]([CH2:31][CH2:32]3)[C:29]([CH3:40])([CH3:39])[C:28]([C:41]3[CH2:59][C:43]5([CH2:46][C:45]([C:53]([O:55]C(C)C)=[O:54])([C:47]([O:49]C(C)C)=[O:48])[CH2:44]5)[CH:42]=3)=[CH:27][CH2:26]4)[CH2:23][CH2:22]2)[S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])=[N:6][CH:7]=1.[OH-].[Na+].Cl>O1CCOCC1.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]([CH2:16][CH2:17][NH:18][C@:19]23[CH2:63][CH2:62][C@@H:61]([C:64]([CH3:66])=[CH2:65])[C@@H:20]2[C@@H:21]2[C@@:34]([CH3:37])([CH2:35][CH2:36]3)[C@@:33]3([CH3:38])[C@@H:24]([C@:25]4([CH3:60])[C@@H:30]([CH2:31][CH2:32]3)[C:29]([CH3:39])([CH3:40])[C:28]([C:41]3[CH2:59][C:43]5([CH2:46][C:45]([C:53]([OH:55])=[O:54])([C:47]([OH:49])=[O:48])[CH2:44]5)[CH:42]=3)=[CH:27][CH2:26]4)[CH2:23][CH2:22]2)[S:9]([C:12]([F:15])([F:14])[F:13])(=[O:11])=[O:10])=[N:6][CH:7]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Step 4 for example A3 was carried out in a similar manner: To a solution of diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(N-(5-chloropyridin-2-yl)-1,1,1-trifluoromethylsulfonamido)ethyl)amino)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylate (32 mg, 0.033 mmol) in dioxane (2 mL) and MeOH (1 mL) was added 1N NaOH (1 mL, 1 mmol). The mixture was stirred at 50° C. for 3 h. The mixture was neutralized by 1N HCl (1 mL) to pH ˜6 and solids formed were collected by filtration. The crude product was purified by preparative HPLC using method 14 to give 6-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13 aR,13bR)-3a-((2-(N-(5-chloropyridin-2-yl)-1,1,1-trifluoromethylsulfonamido)ethyl)amino)-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)spiro[3.3]hept-5-ene-2,2-dicarboxylic acid in 47% yield as a solid. MS: m/e 876.5 (M+H)+, 2.56 min (method 4). 1H NMR (400 MHz, METHANOL-d4) δ 8.53 (d, J=2.3 Hz, 1H), 8.00 (dd, J=8.7, 2.6 Hz, 1H), 7.57 (d, J=8.5 Hz, 1H), 5.92 (s, 1H), 5.54 (dd, J=6.4, 1.9 Hz, 1H), 4.71 (d, J=1.3 Hz, 1H), 4.60 (s, 1H), 4.34-4.17 (m, 2H), 2.76-2.65 (m, 6H), 2.62-2.53 (m, 2H), 2.43-2.33 (m, 1H), 2.15 (dd, J=17.9, 6.7 Hz, 1H), 1.86 (quin, J=10.6 Hz, 1H), 1.79-0.94 (m, 20H), 1.68 (s, 3H), 1.16 (s, 3H), 1.09 (s, 3H), 1.06 (s, 3H), 0.97 (s, 3H), 0.88 (s, 3H). 19F NMR (376 MHz, METHANOL-d4) 6-75.55 (s., 3F).

Workup

customformed
filtrationwere collected by filtration
customThe crude product was purified by preparative HPLC

Sources & evidence

ORD record: ord-c571c75d59954aa6af7acf0a86b34e71
Source dataset: uspto-grants-2014_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08906889B2

Reaction notes

Loading…