Diisopropylethylamine → HCID 118379380, compound

HRID 708516Notes

Reaction equation

HRID 708516 reaction equation
[CH:1]([O:14][C:15]([C:17]1([O:20]/[N:21]=[C:22](/[C:26]2[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[S:29][CH:30]=2)\[C:23](O)=[O:24])[CH2:19][CH2:18]1)=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:39][C@@H:40]1[C:43](=[O:44])[NH:42][C@@H:41]1[CH2:45][N:46]1[N:50]=[C:49]([CH2:51][NH:52][C:53](=[O:59])[O:54][C:55]([CH3:58])([CH3:57])[CH3:56])[C:48]([CH3:60])=[N:47]1.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>CN(C=O)C.CCOC(C)=O>[C:55]([O:54][C:53]([NH:52][CH2:51][C:49]1[C:48]([CH3:60])=[N:47][N:46]([CH2:45][C@@H:41]2[C@H:40]([NH:39][C:23](=[O:24])/[C:22](=[N:21]\[O:20][C:17]3([C:15]([O:14][CH:1]([C:2]4[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=4)[C:8]4[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=4)=[O:16])[CH2:18][CH2:19]3)/[C:26]3[N:27]=[C:28]([NH:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[S:29][CH:30]=3)[C:43](=[O:44])[NH:42]2)[N:50]=1)=[O:59])([CH3:58])([CH3:56])[CH3:57]

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 118380020(Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acidHCID 131733830HCID 131733830, compound

Product 1

HCID 118379380HCID 118379380, compoundYield 82.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (120 mg, 0.213 mmol), tert-butyl ((2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-5-methyl-2H-1,2,3-triazol-4-yl)methyl)carbamate (65.2 mg, 0.210 mmol) and HATU (86 mg, 0.22 mmol) in DMF (2.1 mL) at 0° C., was added DIPEA (0.073 mL, 0.420 mmol). After stirring for 16 h, the reaction mixture was diluted with EtOAc and washed with LiCl solution (5% aq). The aqueous layer was extracted with EtOAc (3×) and the combined organic layers were washed with LiCl solution (5% aq), saturated NaHCO3 (aq), brine, dried over Na2SO4 and concentrated in vacuo. Purification of the crude residue via silica gel chromatography (EtOAc-Heptane, 0-90%) afforded the title compound (144 mg, 82%). LCMS: Rt=1.12 min, m/z=830.5 (M+1) Method 2m_acidic.

Workup

  1. washwashed with LiCl solution (5% aq)
  2. extractionThe aqueous layer was extracted with EtOAc (3×)
  3. washthe combined organic layers were washed with LiCl solution (5% aq), saturated NaHCO3 (aq), brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customPurification of the crude residue via silica gel chromatography (EtOAc-Heptane, 0-90%)

Sources & evidence

ORD record
ord-8d9c8711661e4ea9b035d1fe906044af
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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