Diisopropylethylamine → HCID 86706092, compound

HRID 2176253Notes

Reaction equation

HRID 2176253 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][C:15](/[CH:21]=[CH:22]/[C:23]3([C:29]([OH:31])=[O:30])[CH2:28][CH2:27][CH2:26][CH2:25][O:24]3)=[CH:16][CH:17]=2)[N:12]=1)[CH3:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)C(C)C)(C)C.CC1C=CC=C([N+]([O-])=O)C=1C(OC(=O)C1C([N+]([O-])=O)=CC=CC=1C)=O.[Cl:66][C:67]([Cl:91])([Cl:90])[CH2:68][O:69][C:70]([C@@H:72]1[CH2:77][CH2:76][CH2:75][N:74]([C:78](=[O:89])[C@@H:79]([NH:81][C:82](=[O:88])[C@@H:83](O)[CH:84]([CH3:86])[CH3:85])[CH3:80])[NH:73]1)=[O:71]>CN(C)C1C=CN=CC=1.ClCCl>[Cl:90][C:67]([Cl:66])([Cl:91])[CH2:68][O:69][C:70]([C@@H:72]1[CH2:77][CH2:76][CH2:75][N:74]([C:78](=[O:89])[C@@H:79]([NH:81][C:82](=[O:88])[C@@H:83]([O:30][C:29]([C:23]2(/[CH:22]=[CH:21]/[C:15]3[CH:14]=[C:13]4[C:18]([CH:19]=[CH:20][C:11]([C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH3:10])=[N:12]4)=[CH:17][CH:16]=3)[CH2:28][CH2:27][CH2:26][CH2:25][O:24]2)=[O:31])[CH:84]([CH3:85])[CH3:86])[CH3:80])[NH:73]1)=[O:71]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 104726482-Methyl-6-nitrobenzoic anhydrideHCID 86706052HCID 86706052, compoundHCID 86706091HCID 86706091, compound

Product 1

HCID 86706092HCID 86706092, compoundYield 17.4%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2-{(E)-2-[2-((R)-1-tert-butoxycarbonylamino-ethyl)-quinolin-7-yl]-vinyl}-tetrahydro-pyran-2-carboxylic acid (135 mg, 0.3 mmol), N,N-diisopropylethylamine (96 mg, 0.133 mL, 0.75 mmol), 4-dimethylaminopyridine (80 mg, 0.66 mmol) and 2-methyl-6-nitrobenzoic anhydride (193 mg, 0.56 mmol) in dichloromethane (5 mL) was stirred at 0° C. under nitrogen. A solution of (S)-1-[(S)-2-((S)-2-hydroxy-3-methyl-butyrylamino)-propionyl]-hexahydro-pyridazine-3-carboxylic acid 2,2,2-trichloro-ethyl ester (142 mg, 0.33 mmol) in dichloromethane (2 mL) was added and the reaction mixture was stirred at room temperature for 6 h. The reaction mixture was diluted with dichloromethane and the solution was washed with ice-cold saturated sodium hydrogen carbonate solution, water, ice-cold hydrochloric acid (1 M), water and brine. The organic solution was filtered through a hydrophobic frit and the filtrate was evaporated. The residue was purified by silica gel chromatography using a gradient of iso-hexanes/ethyl acetate 3:1 to 1:3 to afford the title compound (44 mg, 17%) as a white solid and as a 1:1 mixture of two diastereoisomers. LCMS (m/z) 840.2, 842.0 [M+H], Tr=3.75 min.

Workup

  1. washthe solution was washed with ice-cold saturated sodium hydrogen carbonate solution, water, ice-cold hydrochloric acid (1 M), water and brine
  2. filtrationThe organic solution was filtered through a hydrophobic frit
  3. customthe filtrate was evaporated
  4. customThe residue was purified by silica gel chromatography

Sources & evidence

ORD record
ord-8d914002aa154a8187e6c69da0c5d990
Source dataset
uspto-grants-2015_06
Patent number
US09062092B2

Reaction notes

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