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

HRID 708476Notes

Reaction equation

HRID 708476 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].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.[NH2:63][C@@H:64]1[C:67](=[O:68])[NH:66][C@@H:65]1[CH2:69][C:70]1[N:71]=[N:72][N:73]([CH2:75][CH2:76][NH:77][C:78](=[O:84])[O:79][C:80]([CH3:83])([CH3:82])[CH3:81])[CH:74]=1>C(Cl)Cl.CN(C=O)C>[C:80]([O:79][C:78]([NH:77][CH2:76][CH2:75][N:73]1[CH:74]=[C:70]([CH2:69][C@@H:65]2[C@H:64]([NH:63][C:13](=[O:15])/[C:12](=[N:11]\[O:10][C:7]([CH3:8])([CH3:9])[C:6]([O:5][C:1]([CH3:3])([CH3:4])[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]=[N:72]1)=[O:84])([CH3:83])([CH3:81])[CH3:82]

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 118390234Tert-butyl(2-(4-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)carbamate

Product 1

HCID 118380133tert-butyl 2-methyl-2-[(Z)-[2-[[(2R,3S)-2-[[1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]ethyl]triazol-4-yl]methyl]-4-oxoazetidin-3-yl]amino]-1-[2-[(2-methylpropan-2-yl)oxycarbonylamino]-1,3-thiazol-4-yl]-2-oxoethylidene]amino]oxypropanoate

Reagents, catalysts & solvents 1

HCID 22350042dichloromethane N,N-dimethylformamideSolvent

Procedure

Prepared in analogous manner to example 82 step 7, using (Z)-2-(((1-(tert-butoxy)-2-methyl-1-oxopropan-2-yl)oxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (18.55 mg, 0.043 mmol), HATU (17.7 mg, 0.047 mmol), DCM:DMF (1:3, 800 μl), DIPEA (18.86 μl, 0.108 mmol), tert-butyl (2-(4-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-1H-1,2,3-triazol-1-yl)ethyl)carbamate (11.17 mg, 0.036 mmol). 6.5 mg. LCMS: Rt=0.971 min, m/z=722.4 (M+1). Method 2m_acidic. 1H NMR (400 MHz, Methanol-d4) δ 7.82 (s, 1H), 7.32 (s, 1H), 5.34 (d, J=4.9 Hz, 1H), 4.43 (t, J=5.9 Hz, 3H), 4.19 (dt, J=9.3, 4.5 Hz, 1H), 4.09 (q, J=7.1 Hz, 1H), 3.54-3.45 (m, 3H), 3.13 (ddd, J=15.0, 11.8, 6.0 Hz, 2H), 2.93 (dd, J=15.2, 9.6 Hz, 1H), 2.01 (s, 2H), 1.53 (d, J=1.4 Hz, 14H), 1.49 (s, 7H), 1.46 (d, J=1.7 Hz, 15H), 1.38 (s, 14H), 1.23 (t, J=7.1 Hz, 3H).

Workup

  1. customPrepared in analogous manner to example 82 step 7

Sources & evidence

ORD record
ord-369102644003417ba159e54b11e1331c
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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