Hydrochloric Acid → HCID 178502526, compound

HRID 1585097Notes

Reaction equation

HRID 1585097 reaction equation
COC([N:5]([C:13]1[CH:59]=[CH:58][C:16]([C:17]([NH:19][CH2:20][C:21]([N:23]2[CH2:28][CH2:27][N:26]([CH2:29][C:30]([OH:32])=[O:31])[C:25](=[O:33])[C@@H:24]2[CH2:34][CH2:35][CH2:36][NH:37][C:38](=[O:57])[C:39]2[CH:44]=[CH:43][C:42]([N:45](C(OC)=O)[C:46]([NH:48][C:49]([O:51][CH3:52])=[O:50])=[NH:47])=[CH:41][CH:40]=2)=[O:22])=[O:18])=[CH:15][CH:14]=1)[C:6]([NH:8][C:9]([O:11][CH3:12])=[O:10])=[NH:7])=O.[OH-].[Li+].[ClH:62]>CO.O>[ClH:62].[CH3:12][O:11][C:9]([NH:8][C:6](=[NH:7])[NH:5][C:13]1[CH:14]=[CH:15][C:16]([C:17]([NH:19][CH2:20][C:21]([N:23]2[CH2:28][CH2:27][N:26]([CH2:29][C:30]([OH:32])=[O:31])[C:25](=[O:33])[C@@H:24]2[CH2:34][CH2:35][CH2:36][NH:37][C:38](=[O:57])[C:39]2[CH:40]=[CH:41][C:42]([NH:45][C:46]([NH:48][C:49]([O:51][CH3:52])=[O:50])=[NH:47])=[CH:43][CH:44]=2)=[O:22])=[O:18])=[CH:58][CH:59]=1)=[O:10]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 140397742HCID 140397742, compound

Product 1

HCID 178502526HCID 178502526, compoundYield 58%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

In a mixture of 1,4-dioxane (3.0 ml) and H2O (3.0 ml) was dissolved (S)-[4-[(4-guanidinobenzoylamino)acetyl]-3-[3-(4-guanidino-benzoylamino)propyl]-2-oxopiperazin-1-yl]acetic acid hydrochloride (another name: (S)-4-[(4-guanidinobenzoylamino)acetyl]-3-[3-(4-guanidino-benzoylamino)propyl]-2-oxopiperazine-1-acetic acid hydrochloride) (0.3 g, 0.51 mmol) produced in Working Example 15. To the solution were added gradually, under stirring at 0° C. while keeping the pH at 10 or below, a 2N aqueous solution of sodium hydroxide (2.60 ml, 5.10 mmol) and chlorocarbonic acid methyl ester (0.31 ml, 4.00 mmol). The reaction mixture was stirred for 10 minutes at 0° C., whose pH was adjusted to 4 with a 1N aqueous solution of hydrochloric acid, followed by shaking together with ethyl acetate for extraction. The organic layer was dried over anhydrous magnesium sulfate, followed by concentration under reduced pressure. The concentrate was purified by means of a column chromatography (CHP-20, 10% CH3CNaq-15% CH3CNaq-20% CH3CNaq-25% CH3CNaq-35% CH3CNaq) to give (S)-[4-[[4-(1,3-dimethoxycarbonylguanidino)benzoylamino]acetyl]-3-[3-[4-(1,3-dimethoxycarbonylguanidino)benzoylamino]-propyl]-2-oxopiperazin-1-yl]acetic acid (another name: (S)-4-[[4-(1,3-dimethoxycarbonylguanidino)-benzoylamino]acetyl]-3-[3-[4-(1,3-dimethoxycarbonylguanidino)benzoylamino]-propyl]-2-oxopiperazine-1-acetic acid) (0.26 g, 62% ) as a colorless amorphous powdery product. This product (0.26 g, 0.31 mmol) was dissolved in a mixture of methanol (2.6 ml) and H2O (0.26 ml). To the solution was added, under ice-cooling, lithium hydroxide.1.0hydrate (42 mg, 1.00 mmol). One hour later, the reaction system was adjusted to pH 4 with a 1N aqueous solution of hydrochloric acid, followed by concentration under reduced pressure. The concentrate was purified by means of a column chromatography [(CHP-20, 5% CH3CNaq-10% CH3CNaq-15% CH3CNaq-20% CH3CNaq) and (LH-20, H2O)] to afford the title compound (0.13 g, 58% ) as a colorless amorphous powdery product.

Workup

  1. additionTo the solution was added, under ice-
  2. temperaturecooling
  3. customOne hour
  4. concentrationfollowed by concentration under reduced pressure
  5. customThe concentrate was purified by means of a column chromatography [(CHP-20, 5% CH3CNaq-10% CH3CNaq-15% CH3CNaq-20% CH3CNaq) and (LH-20, H2O)]

Sources & evidence

ORD record
ord-943838590ff0425c805cf827cd2d6dbf
Source dataset
uspto-grants-1999_08
Patent number
US05935963

Reaction notes

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