Diisopropylethylamine → tert-butyl 2-methyl-2-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[[(2R,3S)-2-[(5-methyltetrazol-2-yl)methyl]-4-oxoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxypropanoate

HRID 708356Notes

Reaction equation

HRID 708356 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]([OH:15])=O)([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@@H:67]([CH2:68][N:69]2[N:73]=[N:72][C:71]([CH3:74])=[N:70]2)[NH:66][C:65]1=[O:75]>C(Cl)Cl.CN(C=O)C>[C:25]([O:24][C:22]([NH:21][C:18]1[S:19][CH:20]=[C:16](/[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:13]([NH:63][C@@H:64]2[C:65](=[O:75])[NH:66][C@@H:67]2[CH2:68][N:69]2[N:73]=[N:72][C:71]([CH3:74])=[N:70]2)=[O:15])[N:17]=1)=[O:23])([CH3:27])([CH3:28])[CH3:26]

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 189632922-(((1-(tert-Butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 118379665(3S,4R)-3-amino-4-((5-methyl-2H-tetrazol-2-yl)methyl)azetidin-2-one

Product 1

HCID 140689338tert-butyl 2-methyl-2-[(Z)-[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-[[(2R,3S)-2-[(5-methyltetrazol-2-yl)methyl]-4-oxoazetidin-3-yl]amino]-2-oxoethylidene]amino]oxypropanoateYield 100.5%

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent2×

Procedure

Prepared in an analogous manner to example 4, step 3 using (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (130 mg, 0.302 mmol), DIPEA (158 μL, 0.906 mmol) and HATU (138 mg, 0.362 mmol) in DCM:DMF (2:1, 3.0 mL) at 0° C. followed by a solution of (3S,4R)-3-amino-4-((5-methyl-2H-tetrazol-2-yl)methyl)azetidin-2-one (55 mg, 0.30 mmol) in DCM:DMF (2:1, 3.0 mL). After stirring at rt for 1 h it was concentrated in vacuo, dissolved in EtOAc, washed with water then brine, dried over Na2SO4 and concentrated in vacuo. The crude residue was purified via silica gel chromatography (Acetone-DCM), affording the title compound (179 mg, 99%) as a solid. LCMS: Rt=0.93 min, m/z=594.3 (M+1) Method 2m_acidic.

Workup

  1. concentrationwas concentrated in vacuo
  2. dissolutiondissolved in EtOAc
  3. washwashed with water
  4. dry with materialbrine, dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude residue was purified via silica gel chromatography (Acetone-DCM)

Sources & evidence

ORD record
ord-8307ef743af846819eaaf4ec7868768c
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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