N-((1,1-dimethylethoxy)carbonyl)-beta-alanine → HCID 68185403, compound

HRID 2366872Notes

Reaction equation

HRID 2366872 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][CH2:10][C:11]([OH:13])=O)=[O:7])([CH3:4])[CH3:3].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.[C:47]([N:50]1[C:59]2[C:54](=[CH:55][C:56]([C:60]([NH:62]O)=[NH:61])=[CH:57][CH:58]=2)[C@H:53]([NH:64][C:65](=[O:70])[O:66][CH:67]([CH3:69])[CH3:68])[CH2:52][C@@H:51]1[CH3:71])(=[O:49])[CH3:48]>CN(C)C=O>[CH3:69][CH:67]([O:66][C:65](=[O:70])[NH:64][C@H:53]1[C:54]2[C:59](=[CH:58][CH:57]=[C:56]([C:60]3[N:62]=[C:11]([CH2:10][CH2:9][NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[O:13][N:61]=3)[CH:55]=2)[N:50]([C:47](=[O:49])[CH3:48])[C@@H:51]([CH3:71])[CH2:52]1)[CH3:68]

Participants

6

Reactant 4

HCID 76809N-((1,1-dimethylethoxy)carbonyl)-beta-alanineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 178473718HCID 178473718, compound

Product 1

HCID 68185403HCID 68185403, compoundYield 51.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A flask was charged with N-{[(1,1-dimethylethyl)oxy]carbonyl}-β-alanine (227 mg, 1.200 mmol) and HATU (494 mg, 1.300 mmol) then filled with N,N-dimethylformamide (DMF) (5 mL). DIPEA (0.524 mL, 3.00 mmol) was added and the resulting pale yellow solution was stirred for 5 min. 1-Methylethyl {(2S,4R)-1-acetyl-6-[(hydroxyamino)(imino)methyl]-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl}carbamate (for a preparation, see Intermediate 56) (348 mg, 1 mmol) in N,N-dimethylformamide (DMF) (5 mL) was then added via syringe. The resulting mixture was stirred at room temperature for 30 min, at 110° C. for 5 h then cooled to room temperature and partitioned between AcOEt and water/brine (1/1). The layers were separated and the aqueous phase was extracted with AcOEt. The combined organic phases were washed with water/brine (1/1) (3×) then dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using 25 G silica cartridge (gradient: 23 to 73% AcOEt in Hexanes), gave 1-methylethyl((2S,4R)-1-acetyl-6-{5-[2-({[(1,1-dimethylethyl)oxy]carbonyl}amino)ethyl]-1,2,4-oxadiazol-3-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (260 mg, 0.518 mmol, 51.8% yield) as a pale orange foam. LCMS (method G): Retention time 1.04 min, [M+H]+=502.0

Workup

  1. additionwas then added via syringe
  2. stirringThe resulting mixture was stirred at room temperature for 30 min, at 110° C. for 5 h
  3. custompartitioned between AcOEt and water/brine (1/1)
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with AcOEt
  6. washThe combined organic phases were washed with water/brine (1/1) (3×)
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-8a9f187fae59451d808f56f4bfb6955d
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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