N,N-Dimethylethylenediamine → HCID 66571166, compound

HRID 882270Notes

Reaction equation

HRID 882270 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:19]=[CH:18][C:17]([CH2:20][C:21](O)=[O:22])=[CH:16][CH:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=2)[CH2:6][C@@H:5]1[CH3:33])(=[O:3])[CH3:2].[Li].[CH3:35][N:36]([CH3:40])[CH2:37][CH2:38][NH2:39].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.O>[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([CH2:20][C:21]([NH:39][CH2:38][CH2:37][N:36]([CH3:40])[CH3:35])=[O:22])=[CH:18][CH:19]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:24][C:25]2[CH:30]=[CH:29][C:28]([C:31]#[N:32])=[CH:27][N:26]=2)[CH2:6][C@@H:5]1[CH3:33])(=[O:3])[CH3:2]

Participants

9

Reactant 5

HCID 66053N,N-DimethylethylenediamineHCID 81531DiisopropylethylamineHCID 3028194Lithium2×HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 70976470HCID 70976470, compound

Product 1

HCID 66571166HCID 66571166, compoundYield 41%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-(4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)acetic acid, lithium salt (for a preparation see Intermediate 9)(125 mg, 0.284 mmol) and N1,N1-dimethylethane-1,2-diamine (32.5 mg, 0.369 mmol) in DMF (3 mL) were added HATU (162 mg, 0.426 mmol) and DIPEA (0.149 mL, 0.851 mmol). The resulting mixture was stirred at room temperature for 2 h, the reaction mixture was diluted with EtOAc and water. The layers were separated and the aqueous phase was extracted with EtOAc (×3). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The crude residue was dissolved in 1:1 MeOH/DMSO and was purified by MDAP (formate). The appropriate fractions were combined and concentrated in vacuo to give 2-(4-((2S,4R)-1-acetyl-4-((5-cyanopyridin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)phenyl)-N-(2-(dimethylamino)ethyl)acetamide (59 mg, 41%) as a colourless oil. LCMS (Formate, 2 min), Rt=0.65 min, MH+=511.

Workup

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted with EtOAc (×3)
  3. washThe combined organic layers were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe crude residue was dissolved in 1:1 MeOH/DMSO
  8. customwas purified by MDAP (formate)
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-3ba9d8754f274b54bbeb2bc7c5bff0b6
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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