Acetic Acid → diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((3-(1,1-dioxidothiomorpholino)propyl)amino)methyl)-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

HRID 1401018Notes

Reaction equation

HRID 1401018 reaction equation
[CH:1]([C@:3]12[CH2:47][CH2:46][C@@H:45]([C:48]([CH3:50])=[CH2:49])[C@@H:4]1[C@@H:5]1[C@@:18]([CH3:21])([CH2:19][CH2:20]2)[C@@:17]2([CH3:22])[C@@H:8]([C@:9]3([CH3:44])[C@@H:14]([CH2:15][CH2:16]2)[C:13]([CH3:24])([CH3:23])[C:12]([C:25]2[CH2:43][C:27]4([CH2:30][C:29]([C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38])([C:31]([O:33][CH:34]([CH3:36])[CH3:35])=[O:32])[CH2:28]4)[CH:26]=2)=[CH:11][CH2:10]3)[CH2:7][CH2:6]1)=O.C(O)(=O)C.[NH2:55][CH2:56][CH2:57][CH2:58][N:59]1[CH2:64][CH2:63][S:62](=[O:66])(=[O:65])[CH2:61][CH2:60]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.C([O-])(O)=O.[Na+]>[O:65]=[S:62]1(=[O:66])[CH2:61][CH2:60][N:59]([CH2:58][CH2:57][CH2:56][NH:55][CH2:1][C@:3]23[CH2:47][CH2:46][C@@H:45]([C:48]([CH3:50])=[CH2:49])[C@@H:4]2[C@@H:5]2[C@@:18]([CH3:21])([CH2:19][CH2:20]3)[C@@:17]3([CH3:22])[C@@H:8]([C@:9]4([CH3:44])[C@@H:14]([CH2:15][CH2:16]3)[C:13]([CH3:23])([CH3:24])[C:12]([C:25]3[CH2:43][C:27]5([CH2:30][C:29]([C:31]([O:33][CH:34]([CH3:35])[CH3:36])=[O:32])([C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38])[CH2:28]5)[CH:26]=3)=[CH:11][CH2:10]4)[CH2:7][CH2:6]2)[CH2:64][CH2:63]1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 247280544-(3-Aminopropyl)-1lambda~6~,4-thiazinane-1,1-dioneHCID 89734496diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-formyl-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

Product 1

HCID 86692375diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-(((3-(1,1-dioxidothiomorpholino)propyl)amino)methyl)-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-dicarboxylateYield 71.6%

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of diisopropyl 6-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-3a-formyl-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 (100 mg, 0.146 mmol) from Step 3 in DCE (2 mL) was added acetic acid (0.017 mL, 0.291 mmol) and 4-(3-aminopropyl)thiomorpholine 1,1-dioxide (56.0 mg, 0.291 mmol). The mixture was stirred at RT for 2 h, then to the mixture was added sodium triacetoxyborohydride (154 mg, 0.728 mmol) and it was stirred for 24 hours. The mixture was diluted with 7 mL of sat. NaHCO3 and extracted with dichloromethane (3×7 mL). The organic layers were combined and dried with Na2SO4. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The crude product was purified over a silica gel column eluted with mixture of ethyl acetate and hexanes. The fractions containing the expected product were combined to give the title compound as a white solid (90 mg, 71.6% yield). MS: m/e 863.9 (M+H)+, 3.03 min (method 2). 1H NMR (400 MHz, CHLOROFORM-d) δ 5.85 (s, 1H), 5.54-5.43 (m, 1H), 5.14-4.96 (m, 2H), 4.68 (d, J=2.0 Hz, 1H), 4.57 (s, 1H), 3.12-2.90 (m, 9H), 2.83-2.63 (m, 7H), 2.63-2.50 (m, 4H), 2.42 (td, J=11.0, 5.8 Hz, 1H), 2.28-2.17 (m, 1H), 2.13-2.03 (m, 1H), 1.98-1.29 (m, 17H), 1.27-1.18 (m, 16H), 1.13 (s, 3H), 1.09-1.00 (m, 10H), 0.97 (s, 3H), 0.84-0.75 (m, 3H).

Workup

  1. stirringwas stirred for 24 hours
  2. extractionextracted with dichloromethane (3×7 mL)
  3. dry with materialdried with Na2SO4
  4. customThe drying agent was removed by filtration
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customThe crude product was purified over a silica gel column
  7. washeluted with mixture of ethyl acetate and hexanes
  8. additionThe fractions containing the expected product

Sources & evidence

ORD record
ord-d8ba39e64e9a43abb6d78ef2365d50f1
Source dataset
uspto-grants-2014_12
Patent number
US08906889B2

Reaction notes

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