Pyridine → HCID 86760958, compound

HRID 731519Notes

Reaction equation

HRID 731519 reaction equation
[OH:1][CH2:2][CH:3]1[C:15]2[CH:14]=[C:13]([NH:16][C:17](=[S:23])[CH2:18][CH2:19][C:20](=[O:22])[CH3:21])[CH:12]=[CH:11][C:10]=2[C:9]2[C:4]1=[CH:5][CH:6]=[CH:7][CH:8]=2.[OH:24][N:25]1[C:29](=[O:30])[CH2:28][CH2:27][C:26]1=[O:31].[C:32](Cl)(Cl)=[O:33].N1C=CC=CC=1.ClC(Cl)(OC(=O)OC(Cl)(Cl)Cl)Cl>C1COCC1.CCCCCC.C(OCC)(=O)C>[C:20]([CH2:19][CH2:18][C:17]([NH:16][C:13]1[CH:12]=[CH:11][C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[CH:3]([CH2:2][O:1][C:32]([O:24][N:25]3[C:29](=[O:30])[CH2:28][CH2:27][C:26]3=[O:31])=[O:33])[C:15]=2[CH:14]=1)=[S:23])(=[O:22])[CH3:21]

Participants

9

Reactant 5

HCID 1049Pyridine2×HCID 6371PhosgeneHCID 80170N-Hydroxysuccinimide2×HCID 94429TriphosgeneHCID 86760959HCID 86760959, compound2×

Product 1

HCID 86760958HCID 86760958, compoundYield 88%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Intermediate j obtained in step 9(g) was reacted with N-hydroxysuccinimide and phosgene, as depicted in Scheme 4. Thus, pyridine (0.215 ml, 2.7 mmol) was added dropwise to a stirred solution of Intermediate j (0.385 g, 0.9 mmol) and triphosgene (0.265 g, 0.9 mmol, 3 eq) in dry THF (5 ml). After 20 min, the precipitated pyridine hydrochloride salt was filtered out and the THF was removed by evaporation. The obtained oil was dissolved in dry THF (10 ml). N-hydroxysuccinimide (0.5 g, 4.4 mmol, 5 eq) and pyridine (0.215 ml, 2.7 mmol) were then added and the solution stirred for 20 min. The precipitated pyridine hydrochloride salt was filtered out and the THF was removed by vacuum. The obtained oil was further purified by flash chromatography on silica gel column and elution with ethyl acetate:hexane (1:1 and 4:1). The product, Precursor 5, was obtained in a yield of 88% (0.38 g, 0.78 mmol). ESMS: (ca 482) M: 482.2. HPLC (Chromolith column) 6.68 min (10-100% solution B in 10 min, 3 ml/min). TLC (ethyl acetate:hexane, 1:1, v:v) Rf=0.4.

Workup

  1. filtrationthe precipitated pyridine hydrochloride salt was filtered out
  2. customthe THF was removed by evaporation
  3. dissolutionThe obtained oil was dissolved in dry THF (10 ml)
  4. filtrationThe precipitated pyridine hydrochloride salt was filtered out
  5. customthe THF was removed by vacuum
  6. customThe obtained oil was further purified by flash chromatography on silica gel column and elution with ethyl acetate:hexane (1:1 and 4:1)
  7. customThe product, Precursor 5, was obtained in a yield of 88% (0.38 g, 0.78 mmol)

Sources & evidence

ORD record
ord-e2efc7e3d99f4fda93b9a59d64946825
Source dataset
uspto-grants-2009_09
Patent number
US07585837B2

Reaction notes

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