PyBOP → HCID 58724387, compound

HRID 411750Notes

Reaction equation

HRID 411750 reaction equation
Cl.[Cl:2][C:3]1[CH:24]=[N:23][CH:22]=[C:21]([Cl:25])[C:4]=1[C:5]([NH:7][C:8]1[CH:20]=[CH:19][C:11]([CH2:12][C@@H:13]([C:15]([O:17][CH3:18])=[O:16])[NH2:14])=[CH:10][CH:9]=1)=[O:6].F[P-](F)(F)(F)(F)F.N1(O[P+](N2CCCC2)(N2CCCC2)N2CCCC2)C2C=CC=CC=2N=N1>C(Cl)Cl>[Cl:25][C:21]1[CH:22]=[N:23][CH:24]=[C:3]([Cl:2])[C:4]=1[C:5]([NH:7][C:8]1[CH:20]=[CH:19][C:11]([CH2:12][C@@H:13]([C:15]([O:17][CH3:18])=[O:16])[NH2:14])=[CH:10][CH:9]=1)=[O:6]

Participants

4

Reactant 2

HCID 2724699PyBOPHCID 69376873HCID 69376873, compound

Product 1

HCID 58724387HCID 58724387, compoundYield 68.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 0.12 g (0.406 mmol) of 5-(BOC)-1-ethyl-1,4,5,6 -tetrahydropyrrolo[3,4-c]pyrazole-4(S)-carboxylic acid, methyl ester in 2 mL of MeOH was treated with 1 mL of 1N aqueous NaOH. After sonicating the solution for 15 min, it was acidified (pH 2) with 1.2 N HCI and concentrated in vacuo. The residue was diluted with EtOAc and washed with water and brine. The solution was dried over anhydrous Na2SO4 and concentrated in vacuo leaving 0.11 g of a residual oil. This oil was dissolved in 2 mL of CH2Cl2, 0.16 g (0.395 mmol) of 4-(3′,5′-dichloro-isonicotinoyl)amino-(L)-phenylalanine, methyl ester, hydrochloride and 0.17 mL (1.21 mmol) of TEA were added. After all the salt had dissolved, 0.21 g (0.4 mmol) of benzotriazole-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate (PyBOP) was added. After stirring for 4 hr, the reaction was partitioned between CH2Cl2 and water. The organic layer was washed with brine, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel eluted with EtOAc and 5% methanol-EtOAc to afford 5-(BOC)-1-ethyl-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole-4(S)-carbonyl)-4-(3′,5′-dichloroisonicotinoyl)amino-(L)-phenylalanine, methyl ester (99 mg).

Workup

  1. dissolutionAfter all the salt had dissolved
  2. customthe reaction was partitioned between CH2Cl2 and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel
  7. washeluted with EtOAc and 5% methanol-EtOAc

Sources & evidence

ORD record
ord-828f7fc98e264289849f3b743947ce62
Source dataset
uspto-grants-2003_05
Patent number
US06559174B2

Reaction notes

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