Diisopropylethylamine → methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-oxo-2-(thiophen-3-yl)ethyl)(4-(thiophen-3-yl)thiazol-2-yl)amino)-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 85676Notes

Reaction equation

HRID 85676 reaction equation
C[C@]12[C@@]3(C)[C@@H]([C@]4(C)[C@@H](CC3)C(C)(C)C(C3C=CC(C(OC)=O)=CC=3)=CC4)CC[C@@H]1[C@H]1[C@H](C(C)=C)CC[C@]1(NC(N)=S)CC2.C(N(CC)C(C)C)(C)C.Br[CH2:54][C:55]([C:57]1[CH:61]=[CH:60][S:59][CH:58]=1)=[O:56].[CH3:62][C@:63]12[C@@:80]3([CH3:81])[C@@H:71]([C@:72]4([CH3:94])[C@@H:77]([CH2:78][CH2:79]3)[C:76]([CH3:83])([CH3:82])[C:75]([C:84]3[CH:93]=[CH:92][C:87]([C:88]([O:90][CH3:91])=[O:89])=[CH:86][CH:85]=3)=[CH:74][CH2:73]4)[CH2:70][CH2:69][C@@H:68]1[C@H:67]1[C@H:95]([C:98]([CH3:100])=[CH2:99])[CH2:96][CH2:97][C@:66]1([NH:101][C:102]1[S:103][CH:104]=[C:105]([C:107]3[CH:111]=[CH:110][S:109][CH:108]=3)[N:106]=1)[CH2:65][CH2:64]2>CN(C=O)C.O>[CH3:62][C@:63]12[C@@:80]3([CH3:81])[C@@H:71]([C@:72]4([CH3:94])[C@@H:77]([CH2:78][CH2:79]3)[C:76]([CH3:82])([CH3:83])[C:75]([C:84]3[CH:93]=[CH:92][C:87]([C:88]([O:90][CH3:91])=[O:89])=[CH:86][CH:85]=3)=[CH:74][CH2:73]4)[CH2:70][CH2:69][C@@H:68]1[C@H:67]1[C@H:95]([C:98]([CH3:100])=[CH2:99])[CH2:96][CH2:97][C@:66]1([N:101]([CH2:54][C:55](=[O:56])[C:57]1[CH:61]=[CH:60][S:59][CH:58]=1)[C:102]1[S:103][CH:104]=[C:105]([C:107]3[CH:111]=[CH:110][S:109][CH:108]=3)[N:106]=1)[CH2:65][CH2:64]2

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 27763792-Bromo-1-(thiophen-3-yl)ethan-1-oneHCID 86676618methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-thioureido-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)benzoateHCID 86676620methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(4-(thiophen-3-yl)thiazol-2-ylamino)-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

Product 1

HCID 86676619methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-oxo-2-(thiophen-3-yl)ethyl)(4-(thiophen-3-yl)thiazol-2-yl)amino)-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)benzoateYield 82%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-thioureido-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 (150 mg, 0.249 mmol) in DMF (3 mL) was added N,N-diisopropylethylamine (0.217 mL, 1.244 mmol) and 2-bromo-1-(thiophen-3-yl)ethanone (77 mg, 0.373 mmol). The reaction mixture was stirred at rt overnight. After 18 h, the reaction mixture was poured into a separatory funnel containing H2O (5 mL) and extracted with EtOAc (50 mL). The organic layer was washed with brine, dried over MgSO4, filtered and concentrated to white solid. The material was redissolved in DCM (3 mL). MeOH was added and the mixture was concentrated to remove most of DCM. The resulting white precipitate was filtered, washed with cold MeOH, and dried in a vacuum oven to give a 4:1 mixture of (as determined by HPLC integration) methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-1-(prop-1-en-2-yl)-3a-(4-(thiophen-3-yl)thiazol-2-ylamino)-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 and methyl 4-((1R,3aS,5aR,5bR,7aR,11aS,11bR,13aR,13bR)-5a,5b,8,8,11a-pentamethyl-3a-((2-oxo-2-(thiophen-3-yl)ethyl)(4-(thiophen-3-yl)thiazol-2-yl)amino)-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 (134 mg, 82% yield) as white solid. LC/MS: m/e 709.3 (M+H)+, 3.62 min and m/e 833.3 (M+H)+, 2.63 min (method 9), respectively. Reverse phased analytical HPLC showed ratio of major product with rt=16.04 min (m/e 709.3 (M+H)+) to minor product with rt=15.42 min (m/e 833.3 (M+H)+) product of 80%:20% (using analytical HPLC method 2).

Workup

  1. waitAfter 18 h
  2. additionthe reaction mixture was poured into a separatory funnel
  3. extractionextracted with EtOAc (50 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to white solid
  8. dissolutionThe material was redissolved in DCM (3 mL)
  9. additionMeOH was added
  10. concentrationthe mixture was concentrated
  11. customto remove most of DCM
  12. filtrationThe resulting white precipitate was filtered
  13. washwashed with cold MeOH
  14. customdried in a vacuum oven
  15. customto give

Sources & evidence

ORD record
ord-a73a522c49a34ab1af8f57c7884aff8b
Source dataset
uspto-grants-2014_09
Patent number
US08846647B2

Reaction notes

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