Water → (10S)-2-acetylthiomethyl-4-methyl-N-(9-oxo-1,8-diaza-tricyclo[10.6.1.013,18]nonadeca-12(19),13(18),14,16-tetraen-10-yl)pentanamide

HRID 965147Notes

Reaction equation

HRID 965147 reaction equation
[CH3:1][CH:2]([CH3:13])[CH2:3][CH:4]([CH2:8][S:9][C:10](=[O:12])[CH3:11])[C:5]([OH:7])=O.[O:14]=[C:15]1[CH2:32][CH2:31][C:30]2=[CH:33][N:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=32)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][NH:16]1.C1C=CC2N(O)N=[N:40]C=2C=1.O.CCN=C=NCCCN(C)C>CN(C=O)C.C(OCC)(=O)C>[C:10]([S:9][CH2:8][CH:4]([CH2:3][CH:2]([CH3:1])[CH3:13])[C:5]([NH:40][C@H:32]1[CH2:31][C:30]2=[CH:33][N:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:29]=32)[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18][CH2:17][NH:16][C:15]1=[O:14])=[O:7])(=[O:12])[CH3:11]

Participants

8

Reactant 5

HCID 962WaterHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 130175572-[(Acetylthio)methyl]-4-methylpentanoic acidHCID 700960479-Oxo-1,8-diaza-tricyclo[10.6.1.013,18]nonadeca-12(19),13(18),14,16-tetraene

Product 1

HCID 86752869(10S)-2-acetylthiomethyl-4-methyl-N-(9-oxo-1,8-diaza-tricyclo[10.6.1.013,18]nonadeca-12(19),13(18),14,16-tetraen-10-yl)pentanamideYield 85%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-methyl-2-acetylthiomethylpentanoic acid (612 mg, 3 mmol), (10S)-10-amino-(9-oxo-1,8-diaza-tricyclo[10.6.1.013,18 ]nonadeca-12(19),13(18),14,16-tetraene (427 mg, 1.5 mmol), and HOBt.H2O (230 mg, 1.5 mmol) in dry DMF (30 mL) under argon at room temperature was added EDCI (863 mg, 4.5 mmol) in one portion. After stirring overnight, DMF was removed at 30° C. under high vacuum to give a yellowish semi-solid. It was dissolved in ethyl acetate (50 mL), washed with 1N HCl (30 mL), 5% NaHCO3 solution (30 mL) and finally brine (30 mL). The organic layer was dried (MgSO4) and evaporated to dryness. The resulting pale yellow-oil was stirred in 50% ether-pet. ether (40 mL) to yield 600 mg (85%) of (10S)-2-acetylthiomethyl-4-methyl-N-(9-oxo-1,8-diaza-tricyclo[10.6.1.013,18 ]nonadeca-12(19),13(18),14,16-tetraen-10-yl)pentanamide as 1:1 stereoisomeric mixture. The stereoisomeric mixture was separated in flash column chromatography (LPS-2), eluted with 20% ethyl acetate in pet. ether to give the less polar stereoisomer, m.p. 226° C., and the more polar stereoisomer, m.p. 220° C.

Workup

  1. customDMF was removed at 30° C. under high vacuum
  2. customto give a yellowish semi-solid
  3. washwashed with 1N HCl (30 mL), 5% NaHCO3 solution (30 mL) and finally brine (30 mL)
  4. dry with materialThe organic layer was dried (MgSO4)
  5. customevaporated to dryness
  6. stirringThe resulting pale yellow-oil was stirred in 50% ether-pet. ether (40 mL)

Sources & evidence

ORD record
ord-ca929e8e63fd4415ac860a1c5771fb34
Source dataset
uspto-grants-1998_06
Patent number
US05773428

Reaction notes

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