Tetrahydrofuran → ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)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)cyclohex-3-enecarboxylate

HRID 338654Notes

Reaction equation

HRID 338654 reaction equation
[N:1]1([C@:4]23[CH2:40][CH2:39][C@@H:38]([C:41]([CH3:43])=[CH2:42])[C@@H:5]2[C@@H:6]2[C@@:19]([CH3:22])([CH2:20][CH2:21]3)[C@@:18]3([CH3:23])[C@@H:9]([C@:10]4([CH3:37])[C@@H:15]([CH2:16][CH2:17]3)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]3[CH2:31][CH2:30][CH:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:28][CH:27]=3)=[CH:12][CH2:11]4)[CH2:8][CH2:7]2)[CH2:3][CH2:2]1.C([N:47]([CH2:51][CH3:52])[CH:48]([CH3:50])[CH3:49])(C)C.C1C[O:56]CC1>CO.O1CCOCC1>[CH:52]12[CH2:49][CH:48]([N:47]([CH2:2][CH2:3][NH:1][C@:4]34[CH2:40][CH2:39][C@@H:38]([C:41]([CH3:43])=[CH2:42])[C@@H:5]3[C@@H:6]3[C@@:19]([CH3:22])([CH2:20][CH2:21]4)[C@@:18]4([CH3:23])[C@@H:9]([C@:10]5([CH3:37])[C@@H:15]([CH2:16][CH2:17]4)[C:14]([CH3:25])([CH3:24])[C:13]([C:26]4[CH2:31][CH2:30][CH:29]([C:32]([O:34][CH2:35][CH3:36])=[O:33])[CH2:28][CH:27]=4)=[CH:12][CH2:11]5)[CH2:8][CH2:7]3)[CH2:51]1)[CH2:50][O:56]2

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 81531DiisopropylethylamineHCID 86692341ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-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)cyclohex-3-enecarboxylate

Product 1

HCID 86701813ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)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)cyclohex-3-enecarboxylateYield 26%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a vial containing a suspension of ethyl 4-((1R,3 aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(aziridin-1-yl)-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)cyclohex-3-enecarboxylate (0.05 g, 0.085 mmol) in THF (1 mL) was added N,N-diisopropylethylamine (0.089 mL, 0.510 mmol) followed by 2-oxa-5-azabicyclo[2.2.1]heptane, HCl (0.035 g, 0.255 mmol). The vial was sealed and the mixture was heated to 100° C. After 16 h of heating, the mixture was cooled to rt, was diluted with methanol and 1,4-dioxane and was purified by prep HPLC (method 8). The fractions containing the expected product were concentrated under reduced pressure to give ethyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-((2-(2-oxa-5-azabicyclo[2.2.1]heptan-5-yl)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)cyclohex-3-enecarboxylate (0.0152 g, 0.022 mmol, 26.0% yield) as an off-white foam. LCMS: m/e 687.7 (M+H)+, 1.96 min (method 5).

Workup

  1. additionTo a vial containing
  2. customThe vial was sealed
  3. temperatureAfter 16 h of heating
  4. temperaturethe mixture was cooled to rt
  5. customwas purified by prep HPLC (method 8)
  6. additionThe fractions containing the expected product
  7. concentrationwere concentrated under reduced pressure

Sources & evidence

ORD record
ord-f9fceeff17be4156a2442ca9bfa46853
Source dataset
uspto-grants-2014_11
Patent number
US08889854B2

Reaction notes

Loading…