Diisopropylethylamine → 2-methyl-2-propanyl 4-[({(2S,4S)-1-{[1-(N,N'-bis{[(2-methyl-2-propanyl)oxy]carbonyl}carbamimidoyl)-4-piperidinyl]carbonyl}-4-[4-(methylsulfonyl)-1-piperazinyl]-2-pyrrolidinyl}carbonyl)amino]benzoate

HRID 1053815Notes

Reaction equation

HRID 1053815 reaction equation
[CH3:1][S:2]([N:5]1[CH2:10][CH2:9][N:8]([C@@H:11]2[CH2:15][NH:14][C@H:13]([C:16]([NH:18][C:19]3[CH:31]=[CH:30][C:22]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:21][CH:20]=3)=[O:17])[CH2:12]2)[CH2:7][CH2:6]1)(=[O:4])=[O:3].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.[CH3:56][C:57]([O:60][C:61]([NH:63][C:64]([N:73]1[CH2:78][CH2:77][CH:76]([C:79](O)=[O:80])[CH2:75][CH2:74]1)=[N:65][C:66]([O:68][C:69]([CH3:72])([CH3:71])[CH3:70])=[O:67])=[O:62])([CH3:59])[CH3:58].C(N(CC)C(C)C)(C)C>CN(C)C=O>[CH3:72][C:69]([O:68][C:66]([NH:65][C:64]([N:73]1[CH2:78][CH2:77][CH:76]([C:79]([N:14]2[CH2:15][C@@H:11]([N:8]3[CH2:9][CH2:10][N:5]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:6][CH2:7]3)[CH2:12][C@H:13]2[C:16]([NH:18][C:19]2[CH:31]=[CH:30][C:22]([C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])=[CH:21][CH:20]=2)=[O:17])=[O:80])[CH2:75][CH2:74]1)=[N:63][C:61]([O:60][C:57]([CH3:56])([CH3:58])[CH3:59])=[O:62])=[O:67])([CH3:70])[CH3:71]

Participants

6

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 1181076652-methyl-2-propanyl 4-[({(2S,4S)-4-[4-(methylsulfonyl)-1-piperazinyl]-2-pyrrolidinyl}carbonyl)amino]benzoateHCID 1317362991-(N,N'-Bis(tert-butoxycarbonyl)carbamimidoyl)piperidine-4-carboxylic acid

Product 1

HCID 1317363002-methyl-2-propanyl 4-[({(2S,4S)-1-{[1-(N,N'-bis{[(2-methyl-2-propanyl)oxy]carbonyl}carbamimidoyl)-4-piperidinyl]carbonyl}-4-[4-(methylsulfonyl)-1-piperazinyl]-2-pyrrolidinyl}carbonyl)amino]benzoateYield 61%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of the compound prepared in Example 6 (0.2 g, 0.7 mmol) in N,N-dimethylformamide (2 mL) was added 2-(7-aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (0.10 g, 0.26 mmol) at 0° C. After stirring for 20 minutes, the compound prepared in Example 7 (0.12 g, 0.26 mmol) and N,N-diisopropylethylamine (0.15 mL, 0.8 mmol) were added and the reaction stirred at room temperature for 2 h. The reaction was quenched by adding ice cold water and the resulting precipitate was collected by filtration, dried and the crude product purified by flash chromatography to afford the title compound (0.11 g, 61%) as a white solid.

Workup

  1. stirringthe reaction stirred at room temperature for 2 h
  2. customThe reaction was quenched
  3. additionby adding ice cold water
  4. filtrationthe resulting precipitate was collected by filtration
  5. customdried
  6. customthe crude product purified by flash chromatography

Sources & evidence

ORD record
ord-221dc573ccb04182b2680da56cebc2a4
Source dataset
uspto-grants-2016_07
Patent number
US09394250B2

Reaction notes

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