(3R,5S)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino) butanoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate → (2R, 6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylate

HRID 2069178Notes

Reaction equation

HRID 2069178 reaction equation
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][N:5]([C:11]([O:13][C@@H:14]1[CH2:18][C@@H:17]([C:19](=[O:31])[NH:20][C@:21]3([C:26]([O:28][CH2:29][CH3:30])=[O:27])[CH2:23][C@H:22]3C=C)[N:16]([C:32](=[O:61])[C@@H:33]([NH:53][C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:34][CH2:35][N:36]([CH2:49][CH2:50][CH:51]=[CH2:52])[S:37]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=3[N+:46]([O-:48])=[O:47])(=[O:39])=[O:38])[CH2:15]1)=[O:12])[CH2:6]2>C1(C)C=CC=CC=1.ClC1C=CC(OC(C)C)=C(C=1)C=[Ru](Cl)(Cl)C1N(C2C(C)=CC(C)=CC=2C)CCN1C1C(C)=CC(C)=CC=1C>[C:57]([O:56][C:54]([NH:53][C@H:33]1[CH2:34][CH2:35][N:36]([S:37]([C:40]2[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=2[N+:46]([O-:48])=[O:47])(=[O:38])=[O:39])[CH2:49][CH2:50][CH:51]=[CH:52][C@@H:22]2[CH2:23][C@@:21]2([C:26]([O:28][CH2:29][CH3:30])=[O:27])[NH:20][C:19](=[O:31])[C@@H:17]2[CH2:18][C@@H:14]([O:13][C:11]([N:5]3[CH2:4][C:3]4[C:7](=[CH:8][CH:9]=[CH:10][C:2]=4[F:1])[CH2:6]3)=[O:12])[CH2:15][N:16]2[C:32]1=[O:61])=[O:55])([CH3:60])([CH3:58])[CH3:59]

Participants

4

Reactant 1

HCID 59554077(3R,5S)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino) butanoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate

Product 1

HCID 68791570(2R, 6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylate

Reagents, catalysts & solvents 2

HCID 178425459HCID 178425459, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
68 °C

Procedure

(3R,5S)-1-((S)-4-(N-(but-3-enyl)-2-nitrophenylsulfonamido)-2-(tert-butoxycarbonylamino) butanoyl)-5-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)pyrrolidin-3-yl 4-fluoroisoindoline-2-carboxylate (1.65 g, 1.89 mmol) in toluene (400 mL) was degassed by bubbling a stream of nitrogen through the reaction for 1 hr at rt. (5-chloro-2-isopropoxybenzylidene)(1,3-dimesitylimidazolidin-2-yl)ruthenium(V) chloride (0.025 g, 0.038 mmol) was added to the mixture and the mixture was heated to 68° C. (oil bath) and stirred at this temperature for 2 hrs. After removal of solvent, the residue was purified by chromatography (Hexane:Ethyl acetate=1:1) to give (2R, 6S,13aS,14aR,16aS,Z)-ethyl 6-(tert-butoxycarbonylamino)-2-(4-fluoroisoindoline-2-carbonyloxy)-9-(2-nitrophenylsulfonyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa(n)pyrrolo[2,1-c][1,4,9]triazacyclopentadecine-14a-carboxylate as off white solid (1.45 g, 91%). MS: Calcd.: 842. Found: [M+H]+ 843

Workup

  1. customby bubbling a stream of nitrogen
  2. customthrough the reaction for 1 hr at rt
  3. customAfter removal of solvent
  4. customthe residue was purified by chromatography (Hexane:Ethyl acetate=1:1)

Sources & evidence

ORD record
ord-cdbefe7d2f6b4c4cb2194a2dcc6e983c
Source dataset
uspto-grants-2012_10
Patent number
US08299021B2

Reaction notes

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