N,N-Dimethylethylenediamine → HCID 86709415, compound

HRID 882246Notes

Reaction equation

HRID 882246 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:22]=[CH:21][C:17]([C:18](O)=[O:19])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:6][C@@H:5]1[CH3:31])(=[O: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.[CH3:65][N:66]([CH3:70])[CH2:67][CH2:68][NH2:69]>CN(C=O)C>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:18](=[O:19])[NH:69][CH2:68][CH2:67][N:66]([CH3:70])[CH3:65])=[CH:21][CH:22]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[CH2:6][C@@H:5]1[CH3:31])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 66053N,N-DimethylethylenediamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70976510HCID 70976510, compound

Product 1

HCID 86709415HCID 86709415, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask charged with 4-((2S,4R)-1-acetyl-4-((tert-butoxycarbonyl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)benzoic acid (for a preparation see Intermediate 31)(4.88 g, 11.50 mmol) and HATU (5.25 g, 13.80 mmol) was added DMF (2 mL). The resulting mixture was treated with DIPEA (6.02 mL, 34.5 mmol) then after 5 min with N1,N1-dimethylethane-1,2-diamine (1.317 g, 14.95 mmol). After 0.5 h most of the DMF was removed in vacuo. The residue was treated with EtOAc and saturated NaHCO3. Insoluble solid appeared which was isolated by filtration and dried under vacuum at 60° C. for 3 h to give tert-butyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate as white solid (8.5 g), which was used without further purification in the subsequent reaction. The phases of the filtrate were separated, and the aqueous extracted with EtOAc (×2). The combined organic phases were washed with saturated NaHCO3(×3), dried over MgSO4 and concentrated in vacuo to give a liquid (2.1 g). This liquid was loaded onto a SCX cartridge (50 g, pre-conditioned with MeOH) the cartridge washed with MeOH (200 ml) and eluted with ammonia in MeOH (2M, 200 ml). The methanolic ammonia fractions were combined and concentrated in vacuo to give a further portion of tert-butyl ((2S,4R)-1-acetyl-6-(4-((2-(dimethylamino)ethyl)carbamoyl)phenyl)-2-methyl-1,2,3,4-tetrahydroquinolin-4-yl)carbamate (0.3 g, 0.6 mmol, 5% yield) as an orange solid. LCMS (Formate, 2 min), Rt=0.94 min, MH+=495.

Workup

  1. customAfter 0.5 h most of the DMF was removed in vacuo
  2. additionThe residue was treated with EtOAc and saturated NaHCO3
  3. customwas isolated by filtration
  4. customdried under vacuum at 60° C. for 3 h

Sources & evidence

ORD record
ord-a5cfc125c3574910a8ab909cae39439c
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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