N-(tert-butoxycarbonyl)glycine → HCID 68187780, compound

HRID 2366861Notes

Reaction equation

HRID 2366861 reaction equation
[CH3:1][C:2]([O:5][C:6]([NH:8][CH2:9][C:10]([OH:12])=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:46]([N:49]1[C:58]2[C:53](=[CH:54][C:55]([C:59]([NH:61]O)=[NH:60])=[CH:56][CH:57]=2)[C@H:52]([NH:63][C:64](=[O:69])[O:65][CH:66]([CH3:68])[CH3:67])[CH2:51][C@@H:50]1[CH3:70])(=[O:48])[CH3:47]>CN(C)C=O.CCOC(C)=O>[CH3:68][CH:66]([O:65][C:64](=[O:69])[NH:63][C@H:52]1[C:53]2[C:58](=[CH:57][CH:56]=[C:55]([C:59]3[N:61]=[C:10]([CH2:9][NH:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[O:12][N:60]=3)[CH:54]=2)[N:49]([C:46](=[O:48])[CH3:47])[C@@H:50]([CH3:70])[CH2:51]1)[CH3:67]

Participants

7

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 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 68187780HCID 68187780, compoundYield 79%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A flask was charged with N-{[(1,1-dimethylethyl)oxy]carbonyl}glycine (72.4 mg, 0.413 mmol) and HATU (170 mg, 0.448 mmol) then filled with N,N-dimethylformamide (DMF) (2 mL). DIPEA (0.180 mL, 1.033 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) (120 mg, 0.344 mmol) in N,N-dimethylformamide (DMF) (2 mL) was then added via syringe and the resulting mixture was stirred at room temperature for 1 h. The mixture was then stirred at 100° C. under nitrogen for 3.5 h then cooled to room temperature and dissolved in AcOEt. The organic phase was washed with water. The aqueous phase was extracted with AcOEt. The combined organic phases were washed three times with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 on a 10 G silica cartridge (gradient 23 to 63% AcOEt in Hexanes) gave 1-methylethyl((2S,4R)-1-acetyl-6-{5-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-1,2,4-oxadiazol-3-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (132 mg, 0.271 mmol, 79% yield) as a white foam. LCMS (method A): Retention time 1.07 min, [M−H]−=486.23

Workup

  1. additionwas then added via syringe
  2. stirringthe resulting mixture was stirred at room temperature for 1 h
  3. stirringThe mixture was then stirred at 100° C. under nitrogen for 3.5 h
  4. washThe organic phase was washed with water
  5. extractionThe aqueous phase was extracted with AcOEt
  6. washThe combined organic phases were washed three times with water
  7. dry with materialbrine, dried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customPurification of the residue by SP4 on a 10 G silica cartridge (gradient 23 to 63% AcOEt in Hexanes)

Sources & evidence

ORD record
ord-b8f3431e2e104dba9ba28e3c12edd445
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

Loading…