Diisopropylethylamine → tert-butyl ((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate

HRID 1852123Notes

Reaction equation

HRID 1852123 reaction equation
CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:25]([O:29][C:30]([NH:32][C@@H:33]([C@H:45]([CH3:53])[CH2:46][CH:47]([CH3:52])[CH2:48][CH2:49][CH:50]=[CH2:51])[C:34]([N:36]1[CH2:40][C@H:39]([OH:41])[CH2:38][C@H:37]1[C:42]([OH:44])=[O:43])=[O:35])=[O:31])([CH3:28])([CH3:27])[CH3:26].C1(C)C=CC(S(O)(=O)=O)=CC=1.[NH2:65][C@:66]1([C:71]([NH:73][S:74]([CH:77]2[CH2:79][CH2:78]2)(=[O:76])=[O:75])=[O:72])[CH2:68][C@H:67]1[CH:69]=[CH2:70].CCN(C(C)C)C(C)C>C(Cl)Cl>[CH:77]1([S:74]([NH:73][C:71]([C@@:66]23[CH2:68][C@H:67]2[CH:51]=[CH:50][CH2:49][CH2:48][CH:47]([CH3:52])[CH2:46][C@@H:45]([CH3:53])[C@H:33]([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:27])([CH3:26])[CH3:28])[C:34](=[O:35])[N:36]2[CH2:40][C@H:39]([OH:41])[CH2:38][C@H:37]2[C:42](=[O:44])[NH:65]3)=[O:72])(=[O:76])=[O:75])[CH2:79][CH2:78]1.[CH:77]1([S:74]([NH:73][C:71]([C@@:66]2([NH:65][C:42]([C@@H:37]3[CH2:38][C@@H:39]([OH:41])[CH2:40][N:36]3[C:34](=[O:35])[C@@H:33]([NH:32][C:30](=[O:31])[O:29][C:25]([CH3:26])([CH3:28])[CH3:27])[C@H:45]([CH3:53])[CH2:46][CH:47]([CH3:52])[CH2:48][CH2:49][CH:50]=[CH2:51])=[O:43])[CH2:68][C@H:67]2[CH:69]=[CH2:70])=[O:72])(=[O:76])=[O:75])[CH2:79][CH2:78]1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 721632271028252-16-5HCID 86683196(2S,4R)-1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid

Product 2

HCID 89550183tert-Butyl ((2R,6S,7R,13 aS,14aR,16aS,Z)-14a-((cyclopropylsulfonyl)carbamoyl)-2-hydroxy-7,9-dimethyl-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamateHCID 89550268tert-butyl ((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamateYield 187.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

HATU (11.54 g, 30.4 mmol) was added to a solution of (2S,4R)-1-((2S,3R)-2-((tert-butoxycarbonyl)amino)-3,5-dimethylnon-8-enoyl)-4-hydroxypyrrolidine-2-carboxylic acid (10.44 g, 25.3 mmol), (1R,2S)-1-amino-N-(cyclopropylsulfonyl)-2-vinylcyclopropanecarboxamide, p-toluenesulfonate salt (11.17 g, 27.8 mmol), and Hunig's Base (17.67 ml, 101 mmol) in DCM (200 ml) and was stirred at RT for overnight. The reaction was washed with 1N HCl (3×) and then brine and evaporated on rotovap, and purified to get the final product tert-butyl ((2S,3R)-1-((2S,4R)-2-(((1R,2S)-1-((cyclopropylsulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)-4-hydroxypyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (14.8 g, 23.69 mmol, 94% yield) as a light orange foam.

Workup

  1. washThe reaction was washed with 1N HCl (3×)
  2. custombrine and evaporated on rotovap
  3. custompurified

Sources & evidence

ORD record
ord-f06fb1df6e6c42e7b017f2125447d7bc
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Reaction notes

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