Diisopropylethylamine → HCID 118379943, compound

HRID 708529Notes

Reaction equation

HRID 708529 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]([C@@H:51]([N:53]([CH2:61][CH2:62][CH2:63][NH:64][C:65]([O:67][C:68]([CH3:71])([CH3:70])[CH3:69])=[O:66])[C:54](=[O:60])[O:55][C:56]([CH3:59])([CH3:58])[CH3:57])[CH3:52])[CH:48]=[N:47]1.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>C(Cl)Cl.CN(C=O)C.CCOC(C)=O>[C:56]([O:55][C:54]([N:53]([CH2:61][CH2:62][CH2:63][NH:64][C:65]([O:67][C:68]([CH3:70])([CH3:69])[CH3:71])=[O:66])[C@H:51]([C:49]1[CH:48]=[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:13]=[CH:12][CH:11]=[CH:10][CH:9]=4)=[O:16])[CH2:19][CH2:18]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)[CH3:52])=[O:60])([CH3:57])([CH3:58])[CH3:59]

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 118379359HCID 118379359, compoundHCID 118380020(Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid

Product 1

HCID 118379943HCID 118379943, compoundYield 96.3%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 22350042dichloromethane N,N-dimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a mixture of (Z)-2-((1-((benzhydryloxy)carbonyl)cyclopropoxy)imino)-2-(2-((tert-butoxycarbonyl)amino)thiazol-4-yl)acetic acid (416 mg, 0.736 mmol), tert-butyl ((S)-1-(2-(((2R,3S)-3-amino-4-oxoazetidin-2-yl)methyl)-2H-1,2,3-triazol-4-yl)ethyl)(3-((tert-butoxycarbonyl)amino)propyl)carbamate (0.736 mmol) and DIPEA (193 μl, 1.10 mmol) in DCM/DMF (5:1, 7.3 mL) at 0° C. was added HATU (308 mg, 0.810 mmol). After stirring at 0° C. for 1 h it was diluted with EtOAc, washed with water, brine, dried over sodium sulfate and concentrated in vacuo. Purification via silica gel chromatography (EtOAc-Heptane, 50-90%) afforded the desired compound (700 mg, 96%) as a red solid. LCMS: Rt=1.17 min, m/z=987.7 (M+1) Method 2m_acidic. Chiral SFC analysis (SFC-X5, CO2/EtOH=90/10, SFC=5 ml/min, AD column, Rt=12.28 min) confirmed it was a single diastereomer.

Workup

  1. washwashed with water, brine
  2. dry with materialdried over sodium sulfate
  3. concentrationconcentrated in vacuo
  4. customPurification via silica gel chromatography (EtOAc-Heptane, 50-90%)

Sources & evidence

ORD record
ord-52f7d4f37260476ab1c5259e6c41c19a
Source dataset
uspto-grants-2015_11
Patent number
US09174978B2

Reaction notes

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