Methanol → HCID 20583552, compound

HRID 411745Notes

Reaction equation

HRID 411745 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH:21]([C:22]([NH:24][C@H:25]([C:44]([O:46]C)=[O:45])[CH2:26][C:27]3[CH:32]=[CH:31][C:30]([NH:33][C:34](=[O:43])[C:35]4[C:40]([Cl:41])=[CH:39][N:38]=[CH:37][C:36]=4[Cl:42])=[CH:29][CH:28]=3)=[O:23])[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13]2)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1.[OH-].[Na+].CO>>[Cl:1][C:2]1[CH:3]=[C:4]([S:9]([N:12]2[CH:21]([C:22]([NH:24][C@H:25]([C:44]([OH:46])=[O:45])[CH2:26][C:27]3[CH:28]=[CH:29][C:30]([NH:33][C:34](=[O:43])[C:35]4[C:40]([Cl:41])=[CH:39][N:38]=[CH:37][C:36]=4[Cl:42])=[CH:31][CH:32]=3)=[O:23])[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH2:13]2)(=[O:11])=[O:10])[CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

4

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 131723876HCID 131723876, compound

Product 1

HCID 20583552HCID 20583552, compoundYield 72%

Procedure

N-[N-(3,5-Dichlorobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline-3 -carbonyl]-4-(N-(3,5-dichloroisonicotinoyl)amino)-phenylalanine, methyl ester (40 mg, 0.0543 mmol) was treated with a 0.2 N solution of NaOH in MeOH (0.0543 mmol, 0.272 mL). After stirring at rt for 6 h, TLC indicated disappearance of all starting material. The volatiles were removed under reduced pressure and the residue was partitioned between 5% citric acid and EtOAc. The aqueous layer was re-extracted with EtOAc (2X). The organic layers were combined and washed with brine and dried over anhydrous Na2SO4. The crude product was purified by flash column chromatography on silica gel eluted with a gradietn of CH2Cl2 and MeOH to afford N-[N-(3,5-dichlorobenzenesulfonyl)-1,2,3,4-tetrahydroisoquinoline-3-carbonyl]-4 -(N-(3,5-dichloroisonicotinoyl)amino)-phenylalanine (28 mg, 72%) as a white foam, homogeneous by TLC (Rf=0.2 in 9:1 CH2Cl2:MeOH) Mass spectrum (LC/MS ESI) m/e 723 (M+1)+.

Workup

  1. customThe volatiles were removed under reduced pressure
  2. customthe residue was partitioned between 5% citric acid and EtOAc
  3. extractionThe aqueous layer was re-extracted with EtOAc (2X)
  4. washwashed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. customThe crude product was purified by flash column chromatography on silica gel
  7. washeluted with a gradietn of CH2Cl2 and MeOH

Sources & evidence

ORD record
ord-3fb182346c444d138d79948dbe0625dc
Source dataset
uspto-grants-2003_05
Patent number
US06559174B2

Reaction notes

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