Hydrochloric Acid → HCID 14989069, compound

HRID 2380099Notes

Reaction equation

HRID 2380099 reaction equation
C(OC(N[C@H:9]([C:16]([NH:18][C@@H:19]([CH2:36][CH:37]([CH3:39])[CH3:38])[C@@H:20]([OH:35])[CH2:21][C@@H:22]([C:31]([OH:34])([CH3:33])[CH3:32])[C:23]([NH:25][CH2:26][CH:27]([CH3:30])CC)=[O:24])=[O:17])[CH2:10][C:11]1[N:12]=[CH:13][S:14][CH:15]=1)=O)(C)(C)C.Cl.[C:41]([O:45][C:46]([NH:48][C@H:49]([C:61](O)=[O:62])[CH2:50][C:51]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:54]=[CH:53][CH:52]=1)=[O:47])([CH3:44])([CH3:43])[CH3:42].P(C#N)(OCC)(O[CH2:67][CH3:68])=O.C([N:76](CC)CC)C>O1CCOCC1>[C:41]([O:45][C:46]([NH:48][C@H:49]([C:61]([NH:76][C@H:9]([C:16]([NH:18][C@@H:19]([CH2:36][CH:37]([CH3:39])[CH3:38])[C@@H:20]([OH:35])[CH2:21][C@@H:22]([C:31]([OH:34])([CH3:33])[CH3:32])[C:23]([NH:25][CH2:26][CH:27]([CH3:30])[CH2:67][CH3:68])=[O:24])=[O:17])[CH2:10][C:11]1[N:12]=[CH:13][S:14][CH:15]=1)=[O:62])[CH2:50][C:51]1[C:60]2[C:55](=[CH:56][CH:57]=[CH:58][CH:59]=2)[CH:54]=[CH:53][CH:52]=1)=[O:47])([CH3:42])([CH3:44])[CH3:43]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 76257Diethyl cyanophosphonateHCID 7021841Boc-3-(1-naphthyl)-L-alanineHCID 86748258HCID 86748258, compound

Product 1

HCID 14989069HCID 14989069, compoundYield 95%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 142 mg (0.25 mmoles) of (2S, 4S, 5S)-5-{N-[N-(t-butoxycarbonyl)-3-(4-thiazolyl)-L-alanyl]}amino-4-hydroxy-2-(1-hydroxy-1-methylethyl)-7-methyl-N-[2(RS)-methylbutyl]octanamide (prepared as described in Example 6) in 5 ml of a 4N solution of hydrogen chloride in dioxane was stirred at room temperature for 30 minutes. At the end of this time, the solvent was removed by distillation under reduced pressure. Diethyl ether was then added to the residue, and the solvent was removed again by distillation under reduced pressure. This operation was repeated in total three times, after which the residue was dried under vacuum for 8 hours. At the end of this time, the dried material was suspended in 10 ml of anhydrous tetrahydrofuran, and 99.9 mg (0.32 mmoles) of N-t-butoxycarbonyl-3-(1 naphthyl)-L-alanine were added to the resulting suspension, followed by 0.05 ml (0.33 mmoles) of 95% diethyl cyanophosphate and 0.12 ml (0.86 mmoles) of triethylamine, all whilst ice-cooling and under an atmosphere of nitrogen, The mixture was then stirred for 8 hours, after which the solvent was removed by distillation under reduced pressure, and the residue was purified by silica gel thin layer chromatography (using a 10:1 by volume mixture of methylene chloride and methanol as developing solvent), to give 181 mg (yield 95%) of the title compound as white crystals, melting at 90°-92° C.

Workup

  1. customAt the end of this time, the solvent was removed by distillation under reduced pressure
  2. additionDiethyl ether was then added to the residue
  3. customthe solvent was removed again by distillation under reduced pressure
  4. customafter which the residue was dried under vacuum for 8 hours
  5. temperatureall whilst ice-cooling and under an atmosphere of nitrogen
  6. stirringThe mixture was then stirred for 8 hours
  7. customafter which the solvent was removed by distillation under reduced pressure
  8. customthe residue was purified by silica gel thin layer chromatography (
  9. additionby volume mixture of methylene chloride and methanol as developing solvent),

Sources & evidence

ORD record
ord-5838f0dbd76a49119202cbcbfa847a58
Source dataset
uspto-grants-1994_11
Patent number
US05364844

Reaction notes

Loading…