Diisopropylethylamine → HCID 69287829, compound

HRID 1766841Notes

Reaction equation

HRID 1766841 reaction equation
[C:1]([C:5]1[S:9][C:8]([NH2:10])=[N:7][N:6]=1)([CH3:4])([CH3:3])[CH3:2].[Li].[CH2:12]([O:19][C:20]([NH:22][CH2:23][C@H:24]([NH:30][C:31](=[O:36])[CH2:32][C:33](O)=[O:34])[C@@H:25]([OH:29])[C:26]#[C:27][CH3:28])=[O:21])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1.C(N(CC)C(C)C)(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CN(C=O)C>[CH2:12]([O:19][C:20](=[O:21])[NH:22][CH2:23][C@H:24]([NH:30][C:31](=[O:36])[CH2:32][C:33](=[O:34])[NH:10][C:8]1[S:9][C:5]([C:1]([CH3:4])([CH3:3])[CH3:2])=[N:6][N:7]=1)[C@@H:25]([OH:29])[C:26]#[C:27][CH3:28])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 170170ButhidazolamineHCID 3028194LithiumHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 69287489HCID 69287489, compound

Product 1

HCID 69287829HCID 69287829, compoundYield 43%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

The compound 5-tert-butyl-[1,3,4]thiadiazol-2-ylamine (67 mg, 0.43 mmol) was dissolved in 6 mL of 1:1 CH2Cl2/DMF. The resultant solution was charged sequentially with the lithium salt of N-[(1S,2S)-1-(benzyloxycarbonylamino-methyl)-2-hydroxy-pent-3-ynyl]-malonamic acid (151 mg, 0.43 mmol, see procedure 21a), N, N-diisopropylethylamine (0.38 mL, 2.1 mmol) and HATU (194 mg, 0.51 mmol). The mixture was stirred for 12 h at RT, concentrated in vacuo, and partitioned between EtOAc and sat. NH4Cl. The aqueous phase was extracted with EtOAc (1×). The combined organic extracts were washed with sat. NaHCO3 and brine, dried (Na2SO4), filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford {(2S,3S)-2-[2-(5-tert-butyl-[1,3,4]thiadiazol-2-ylcarbamoyl)-acetylamino]-3-hydroxy-hex-4-ynyl}-carbamic acid benzyl ester as a colorless oil (90 mg, 43% yield). MS found: (M+Na)+=510.4.

Workup

  1. concentrationconcentrated in vacuo
  2. custompartitioned between EtOAc and sat. NH4Cl
  3. extractionThe aqueous phase was extracted with EtOAc (1×)
  4. washThe combined organic extracts were washed with sat. NaHCO3 and brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography

Sources & evidence

ORD record
ord-be8f2d854c7140c4a480a10d4d6516ea
Source dataset
uspto-grants-2007_06
Patent number
US07230133B2

Reaction notes

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