Ethanolamine → HCID 71469143, compound

HRID 882268Notes

Reaction equation

HRID 882268 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].[CH2:35]([CH2:37][NH2:38])[OH:36].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:38][CH2:37][CH2:35][OH:36])=[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 700EthanolamineHCID 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 71469143HCID 71469143, compoundYield 11%

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 (Intermediate 9)(166 mg, 0.377 mmol) and ethanolamine (0.034 mL, 0.565 mmol) in DMF (3 mL) were added HATU (287 mg, 0.754 mmol) and DIPEA (0.197 mL, 1.131 mmol). The resulting mixture was stirred at room temperature for 1 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-hydroxyethyl)acetamide (21 mg, 11%) as a colourless oil. LCMS (Formate, 2 min), Rt=0.76 min, MH+=484.

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-cce91a584e32429ea8e99ab50ca39a2b
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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