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 338654ノート

反応式

HRID 338654 の反応式
[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

参加物

6

反応物 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

生成物 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-enecarboxylate収率 26%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-f9fceeff17be4156a2442ca9bfa46853
出典データセット
uspto-grants-2014_11
特許番号
US08889854B2

反応ノート

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