Diisopropylethylamine → HCID 139298657, compound

HRID 708366Notes

Reaction equation

HRID 708366 reaction equation
[C:1]([O:5][C:6](=[O:29])[C:7]([O:10]/[N:11]=[C:12](/[C:16]1[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=1)\[C:13](O)=[O:14])([CH3:9])[CH3:8])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH2:63][C@@H:64]1[C:67](=[O:68])[NH:66][C@@H:65]1[CH2:69][N:70]1[CH:74]=[N:73][C:72]([CH2:75][NH:76][C:77](=[O:83])[O:78][C:79]([CH3:82])([CH3:81])[CH3:80])=[N:71]1>C(Cl)Cl.CN(C=O)C.O.CCOC(C)=O>[C:79]([O:78][C:77]([NH:76][CH2:75][C:72]1[N:73]=[CH:74][N:70]([CH2:69][C@@H:65]2[C@H:64]([NH:63][C:13](=[O:14])/[C:12](=[N:11]\[O:10][C:7]([CH3:9])([CH3:8])[C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:29])/[C:16]3[N:17]=[C:18]([NH:21][C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[S:19][CH:20]=3)[C:67](=[O:68])[NH:66]2)[N:71]=1)=[O:83])([CH3:80])([CH3:82])[CH3:81]

Participants

7

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 189632922-(((1-(tert-Butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 131733733HCID 131733733, compound

Product 1

HCID 139298657HCID 139298657, compoundYield 554.8%

Reagents, catalysts & solvents 2

HCID 22350042dichloromethane N,N-dimethylformamideSolvent2×HCID 22728543Water ethylacetateSolvent

Procedure

To a slurry of (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (47 mg, 0.109 mmol) in DCM:DMF (12:1, 6.5 mL) at 0° C. was added DIPEA (505 μL, 2.89 mmol) followed by HATU (440 mg, 1.16 mmol). To the resulting solution was added a solution of tert-butyl ((1-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-1H-1,2,4-triazol-3-yl)methyl)carbamate (286 mg, 0.964 mmol) in DCM:DMF (14:1, 7.5 mL). After 1 h of stirring it was diluted with water/EtOAc and the layers separated. The aqueous layer was extracted with EtOAc and the combined organic layers were washed with brine (3×), dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (Acetone-DCM, 70%) to afford the title compound (428 mg, 63%). LCMS: Rt=0.99 min, m/z=708.2 (M+1) Method 2m_acidic.

Workup

  1. customthe layers separated
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic layers were washed with brine (3×)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (Acetone-DCM, 70%)

Sources & evidence

ORD record
ord-f73e4834d18a4c068cb8c76e1c3369cc
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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