p-Toluenesulfonic acid → tert-butyl (3S,13R,15S,E)-13-(biphenyl-4-yl)-15-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-en-3-ylcarbamate

HRID 1666974Notes

Reaction equation

HRID 1666974 reaction equation
[C:1]1([C:35]2C=CC=CC=2)[CH:6]=[CH:5][C:4]([C@@:7]23[CH2:25][N:19]([C@H:20]([C:22]([OH:24])=O)[CH2:21]2)[C:18](=[O:26])[C@@H:17]([NH:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH:11]=[CH:10][CH2:9][S:8]3)=[CH:3][CH:2]=1.[NH2:41][C@:42]1([C:47]([NH:49][S:50]([CH:53]2[CH2:55][CH2:54]2)(=[O:52])=[O:51])=[O:48])[CH2:44][C@H:43]1[CH:45]=[CH2:46].C[C:57]1[CH:58]=[CH:59]C(S(O)(=O)=O)=[CH:61][CH:62]=1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(CC)C(C)C)(C)C>C(Cl)Cl.CCOC(C)=O>[C:1]1([C:35]2[CH:59]=[CH:58][CH:57]=[CH:62][CH:61]=2)[CH:6]=[CH:5][C:4]([C@@:7]23[CH2:25][N:19]([C@H:20]([C:22](=[O:24])[NH:41][C@:42]4([C:47](=[O:48])[NH:49][S:50]([CH:53]5[CH2:55][CH2:54]5)(=[O:52])=[O:51])[CH2:44][C@H:43]4[CH:45]=[CH2:46])[CH2:21]2)[C:18](=[O:26])[C@@H:17]([NH:27][C:28](=[O:29])[O:30][C:31]([CH3:33])([CH3:32])[CH3:34])[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH:11]=[CH:10][CH2:9][S:8]3)=[CH:3][CH:2]=1

Participants

8

Reactant 5

HCID 6101p-Toluenesulfonic acidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 23595125(1R,2S)-1-Amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamideHCID 67443912(3S,13R,15S,Z)-13-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-ene-15-carboxylic acid

Product 1

HCID 45102643tert-butyl (3S,13R,15S,E)-13-(biphenyl-4-yl)-15-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-en-3-ylcarbamateYield 52.5%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To an iced slurry of (3S,13R,15S,Z)-13-(biphenyl-4-yl)-3-(tert-butoxycarbonylamino)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-ene-15-carboxylic acid (28 mg, 0.050 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, pTSA, 0.68H2O (25.7 mg, 0.062 mmol), and HATU (28.5 mg, 0.075 mmol) in DCM (1 mL) was added N,N-Diisopropylethylamine (0.043 mL, 0.248 mmol). The formed light brown solution was stirred at room temperature overnight. Diluted with EtOAc, washed it with 5% citric acid, and brine, dried over MgSO4, filtered, evaporated. The formed residue was purified by prep-HPLC to afford the desired product tert-butyl (3S,13R,15S,E)-13-(biphenyl-4-yl)-15-((1R,2S)-1-(cyclopropylsulfonylcarbamoyl)-2-vinylcyclopropylcarbamoyl)-2-oxo-12-thia-1-azabicyclo[11.2.1]hexadec-9-en-3-ylcarbamate (22 mg, 0.026 mmol, 52.5% yield) as a white solid.

Workup

  1. washwashed it with 5% citric acid, and brine
  2. dry with materialdried over MgSO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe formed residue was purified by prep-HPLC

Sources & evidence

ORD record
ord-9c02057d736a491b9589143fc43ac406
Source dataset
uspto-grants-2011_10
Patent number
US08044087B2

Reaction notes

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