Hydrochloric Acid → (S)-2-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methoxycarbonyl-methyl)-carbamoyl]-2-methyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-pentanoic acid tert-butyl ester

HRID 2242440Notes

Reaction equation

HRID 2242440 reaction equation
[CH3:1][O:2][C:3](=[O:29])[C@@H:4]([NH:11][C:12](=[O:28])[C@@H:13]([NH:17][C:18]([O:20]CC1C=CC=CC=1)=O)[CH:14]([CH3:16])[CH3:15])[CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.COC([C@@H:34]1[CH2:38][C@H:37]([O:39][C:40]2[C:49]3[C:44](=[CH:45][C:46]([O:50][CH3:51])=[CH:47][CH:48]=3)[N:43]=[C:42]([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH:41]=2)[CH2:36][C@H:35]1[C:58](=[O:71])[NH:59][C@H:60]([C:64]([O:66][C:67]([CH3:70])([CH3:69])[CH3:68])=[O:65])[CH2:61][CH2:62][CH3:63])=O.[Li+].[OH-].Cl>C(O)C.O1CCOCC1.O.[Pd]>[C:67]([O:66][C:64](=[O:65])[C@@H:60]([NH:59][C:58]([C@@H:35]1[CH2:36][C@@H:37]([O:39][C:40]2[C:49]3[C:44](=[CH:45][C:46]([O:50][CH3:51])=[CH:47][CH:48]=3)[N:43]=[C:42]([C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=3)[CH:41]=2)[CH2:38][C@H:34]1[C:18](=[O:20])[NH:17][C@H:13]([C:12](=[O:28])[NH:11][C@@H:4]([CH:5]1[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10]1)[C:3]([O:2][CH3:1])=[O:29])[CH:14]([CH3:15])[CH3:16])=[O:71])[CH2:61][CH2:62][CH3:63])([CH3:68])([CH3:69])[CH3:70]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 57892932(S)-((S)-2-Benzyloxycarbonylamino-3-methyl-butyrylamino)-cyclohexyl-acetic acid methyl esterHCID 59204183(1R,2R,4R)-2-((S)-1-tert-Butoxycarbonyl-butylcarbamoyl)-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarboxylic acid methyl ester

Product 1

HCID 11274400(S)-2-{[(1R,2R,4S)-2-{(S)-1-[((S)-Cyclohexyl-methoxycarbonyl-methyl)-carbamoyl]-2-methyl-propylcarbamoyl}-4-(7-methoxy-2-phenyl-quinolin-4-yloxy)-cyclopentanecarbonyl]-amino}-pentanoic acid tert-butyl esterYield 88%

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

To a solution of 55 (40 mg, 0.099 mmol) in ethanol (95%) (7.5 mL) was added palladium on active carbon (10%, 40 mg) and the mixture was hydrogenated under pressure at room temperature for 2 h. The mixture was filtered through celite and evaporated. Compound 43 (38 mg, 0.083 mmol) was dissolved in dioxane/H2O 1:1 (3 mL) and the mixture was cooled to 0° C. before 1 M LiOH (140 μL, 0.140 mmol) was added to the stirred solution. After 1 h the mixture was neutralized with 1 M hydrochloric acid and the solvent was evaporated and co-evaporated with toluene. The residue was coupled to deprotected 55 using the same HATU coupling conditions as in the synthesis of compound 48. Purification by HPLC (MeOH/H2O 90:10 with 0.2% triethylamine) gave 56 (56 mg, 88%) as a colorless solid.

Workup

  1. filtrationThe mixture was filtered through celite
  2. customevaporated
  3. additionwas added to the stirred solution
  4. customthe solvent was evaporated
  5. customas in the synthesis of compound 48
  6. customPurification by HPLC (MeOH/H2O 90:10 with 0.2% triethylamine)

Sources & evidence

ORD record
ord-4e7232ccdedf4a748d0949882738ace9
Source dataset
uspto-grants-2010_03
Patent number
US07671032B2

Reaction notes

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