Diisopropylethylamine → HCID 68187784, compound

HRID 2366863Notes

Reaction equation

HRID 2366863 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]([OH:16])=O)=[CH:11][CH:12]=2)[C@H:7]([NH:17][C:18]([O:20][CH:21]([CH3:23])[CH3:22])=[O:19])[CH2:6][C@@H:5]1[CH3:24])(=[O:3])[CH3:2].CN(C(ON1N=NC2[CH:36]=[CH:37][CH:38]=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[CH3:49]CN(C(C)C)C(C)C.CC([N:62]([CH2:66][C:67]([NH:69]O)=[NH:68])[C:63](=[O:65])[O-:64])(C)C>CN(C)C=O>[CH3:23][CH:21]([O:20][C:18](=[O:19])[NH:17][C@H:7]1[C:8]2[C:13](=[CH:12][CH:11]=[C:10]([C:14]3[O:16][N:68]=[C:67]([CH2:66][NH:62][C:63]([O:64][C:37]([CH3:36])([CH3:38])[CH3:49])=[O:65])[N:69]=3)[CH:9]=2)[N:4]([C:1](=[O:3])[CH3:2])[C@@H:5]([CH3:24])[CH2:6]1)[CH3:22]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67195816HCID 67195816, compoundHCID 178449097HCID 178449097, compound

Product 1

HCID 68187784HCID 68187784, compoundYield 47.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

A flask was charged with (2S,4R)-1-acetyl-2-methyl-4-({[(1-methylethyl)oxy]carbonyl}amino)-1,2,3,4-tetrahydro-6-quinolinecarboxylic acid (for a preparation, see Intermediate 63) (100 mg, 0.3 mmol) and HATU (137 mg, 0.360 mmol) then filled with N,N-dimethylformamide (DMF) (2 mL) and the mixture was treated with DIPEA (0.157 mL, 0.900 mmol). The resulting mixture was stirred at room temperature for 5 min then 1,1-dimethylethyl[2-(hydroxyamino)-2-iminoethyl]carbamate (for a preparation, see Intermediate 64) (68.1 mg, 0.360 mmol) in N,N-dimethylformamide (DMF) (2 mL) was added. The resulting mixture was stirred at room temperature under nitrogen for 30 min, at 110° C. for 7 h then cooled to room temperature. The mixture was partitioned between AcOEt and water and the phases were separated. The aqueous phase was extracted three times with AcOEt and the combined organic phases were washed twice with water then brine, dried over MgSO4 and concentrated in vacuo. Purification of the residue by SP4 using a 10 G silica cartridge (gradient: 8 to 38% (10% MeOH in DCM) in DCM) gave 1-methylethyl((2S,4R)-1-acetyl-6-{3-[({[(1,1-dimethylethyl)oxy]carbonyl}amino)methyl]-1,2,4-oxadiazol-5-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate (70 mg, 0.144 mmol, 47.9% yield) as a pale yellow solid.

Workup

  1. customfor a preparation
  2. additionwas added
  3. stirringThe resulting mixture was stirred at room temperature under nitrogen for 30 min, at 110° C. for 7 h
  4. temperaturethen cooled to room temperature
  5. customThe mixture was partitioned between AcOEt and water
  6. customthe phases were separated
  7. extractionThe aqueous phase was extracted three times with AcOEt
  8. washthe combined organic phases were washed twice with water
  9. dry with materialbrine, dried over MgSO4
  10. concentrationconcentrated in vacuo
  11. customPurification of the residue by SP4

Sources & evidence

ORD record
ord-5b7bb34321534c61bce1088123d7ade9
Source dataset
uspto-grants-2014_04
Patent number
US08697725B2

Reaction notes

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