Diisopropylethylamine → HCID 178454252, compound

HRID 708499Notes

Reaction equation

HRID 708499 reaction equation
[NH2:1][C@@H:2]1[C:5](=[O:6])[NH:4][C@@H:3]1[CH2:7][N:8]1[N:12]=[C:11]([CH2:13][NH:14][C:15](=[N:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[N:16]([CH2:24][CH:25]2[CH2:28][N:27]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:26]2)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]=[N:9]1.[CH:44]([O:57][C:58]([C:60]1([O:63]/[N:64]=[C:65](/[C:69]2[N:70]=[C:71]([NH:74][C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[S:72][CH:73]=2)\[C:66](O)=[O:67])[CH2:62][CH2:61]1)=[O:59])([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=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.C(Cl)Cl.CCOC(C)=O>[CH:44]([O:57][C:58]([C:60]1([O:63]/[N:64]=[C:65](/[C:69]2[N:70]=[C:71]([NH:74][C:75]([O:77][C:78]([CH3:81])([CH3:80])[CH3:79])=[O:76])[S:72][CH:73]=2)\[C:66]([NH:1][C@@H:2]2[C:5](=[O:6])[NH:4][C@@H:3]2[CH2:7][N:8]2[N:12]=[C:11]([CH2:13][NH:14][C:15](=[N:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[N:16]([CH2:24][CH:25]3[CH2:26][N:27]([C:29]([O:31][C:32]([CH3:34])([CH3:33])[CH3:35])=[O:30])[CH2:28]3)[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH:10]=[N:9]2)=[O:67])[CH2:62][CH2:61]1)=[O:59])([C:51]1[CH:52]=[CH:53][CH:54]=[CH:55][CH:56]=1)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1

Participants

8

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 178454254HCID 178454254, compound

Product 1

HCID 178454252HCID 178454252, compoundYield 58%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of tert-butyl 3-((3-((2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2H-1,2,3-triazol-4-yl)methyl)-1,2-bis(tert-butoxycarbonyl)guanidino)methyl)azetidine-1-carboxylate (309 mg, 0.51 mmol) and (Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (273 mg, 0.51 mmol) in DMF (6 mL, ratio: 1) and DCM (6 mL, ratio: 1) was added HATU (232 mg, 0.61 mmol) followed by DIPEA (0.22 mL, 1.27 mmol). After stirring at rt for 12 h, EtOAc was added to the reaction mixture and washed with water, brine, dried over Na2SO4, filtered and concentrated in vacuo. The crude residue was purified via silica gel chromatography (EtOAc-heptane, 0-95%) to afford the title compound (330 mg, 58%). LCMS: Rt=1.15 min, m/z=1127.8 (M+1) Method 2m_acidic.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe crude residue was purified via silica gel chromatography (EtOAc-heptane, 0-95%)

Sources & evidence

ORD record
ord-b553b75f32e64b7eab7813dbe6105e30
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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