Hydrochloric Acid → ethyl (1R,2S)-1-{[(4S)-4-{[(4-bromophenyl)sulfonyl]oxy}-1-{(2S)-2-[(tert-butoxycarbonyl)amino]non-8-enoyl}-L-prolyl]amino}-2-ethenylcyclopropanecarboxylate

HRID 522364Notes

Reaction equation

HRID 522364 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]([CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH:42]=[CH2:43])[C:34]([OH:36])=O)=[O:31])([CH3:28])([CH3:27])[CH3:26].[Br:44][C:45]1[CH:50]=[CH:49][C:48]([S:51]([O:54][C@@H:55]2[CH2:59][NH:58][C@H:57]([C:60]([NH:62][C@:63]3([C:68]([O:70][CH2:71][CH3:72])=[O:69])[CH2:65][C@H:64]3[CH:66]=[CH2:67])=[O:61])[CH2:56]2)(=[O:53])=[O:52])=[CH:47][CH:46]=1.CCN(C(C)C)C(C)C.Cl>CN(C=O)C>[Br:44][C:45]1[CH:50]=[CH:49][C:48]([S:51]([O:54][C@@H:55]2[CH2:59][N:58]([C:34](=[O:36])[C@@H:33]([NH:32][C:30]([O:29][C:25]([CH3:26])([CH3:27])[CH3:28])=[O:31])[CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH:42]=[CH2:43])[C@H:57]([C:60]([NH:62][C@:63]3([C:68]([O:70][CH2:71][CH3:72])=[O:69])[CH2:65][C@H:64]3[CH:66]=[CH2:67])=[O:61])[CH2:56]2)(=[O:52])=[O:53])=[CH:47][CH:46]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11507316(2S)-N-Boc-amino-non-8-enoic acidHCID 117598982HCID 117598982, compound

Product 1

HCID 117598808ethyl (1R,2S)-1-{[(4S)-4-{[(4-bromophenyl)sulfonyl]oxy}-1-{(2S)-2-[(tert-butoxycarbonyl)amino]non-8-enoyl}-L-prolyl]amino}-2-ethenylcyclopropanecarboxylateYield 83.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

HATU (27.3 g) was added to the solution of (2S)-2-[(tert-butoxycarbonyl)amino]non-8-enoic acid (19.5 g) in DMF (100 ml) and the solution was stirred 15 minutes. The reaction mixture was cooled to 0° C. Then, the amine from Step 3 (31.8 g) in DMF (200 ml) (cooled to 0° C.) was added followed by DIPEA (11.40 ml). The solution was stirred at 0° C. for 1 hour. Hydrochloric acid (1M) was added and the mixture was extracted with diethyl ether (3×). The combined organic fractions were washed with brine, dried over magnesium sulfate, filtered and concentrated. The residue was purified by flash chromatography (ISCO, 0 to 100% ethyl acetate in hexanes) to give the desired product (40.2 g) as a white foam. LRMS (ES+) m/z 762.2 (M+Na)+.

Workup

  1. stirringThe solution was stirred at 0° C. for 1 hour
  2. extractionthe mixture was extracted with diethyl ether (3×)
  3. washThe combined organic fractions were washed with brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (ISCO, 0 to 100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-017ae488c8bd4b6b963c169631e42383
Source dataset
uspto-grants-2016_05
Patent number
US09328138B2

Reaction notes

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