Ethanolamine → 5-((2S,4R)-1-acetyl-4-((5-cyanopyrazin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-hydroxyethyl)picolinamide

HRID 882291Notes

Reaction equation

HRID 882291 reaction equation
[C:1]([N:4]1[C:13]2[C:8](=[CH:9][C:10]([C:14]3[CH:15]=[CH:16][C:17]([C:20]([OH:22])=O)=[N:18][CH:19]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[N:28][C:27]([C:30]#[N:31])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[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.[NH2:66][CH2:67][CH2:68][OH: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:20]([NH:66][CH2:67][CH2:68][OH:69])=[O:22])=[N:18][CH:19]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[N:28][C:27]([C:30]#[N:31])=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:32])(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 700EthanolamineHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 867094225-((2S,4R)-1-acetyl-4-((5-cyanopyrazin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinic acid

Product 1

HCID 714682585-((2S,4R)-1-acetyl-4-((5-cyanopyrazin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-hydroxyethyl)picolinamideYield 38%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

5-((2S,4R)-1-acetyl-4-((5-cyanopyrazin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)picolinic acid (for a preparation see Intermediate 53) (100 mg, 0.233 mmol), HATU (177 mg, 0.467 mmol) and DIPEA (0.122 ml, 0.700 mmol) were combined in DMF (3 mL) and stirred at room temperature for 10 mins. 2-aminoethanol (0.029 ml, 0.350 mmol) was added and the reaction mixture stirred for 1.5 h. The mixture was concentrated in vacuo and purified by MDAP (formate) to give 5-((2S,4R)-1-acetyl-4-((5-cyanopyrazin-2-yl)amino)-2-methyl-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-hydroxyethyl)picolinamide (42 mg, 0.089 mmol, 38% yield). LCMS: (Formate, 2 min), Rt=0.73 mins, MH+=472

Workup

  1. stirringthe reaction mixture stirred for 1.5 h
  2. concentrationThe mixture was concentrated in vacuo
  3. custompurified by MDAP (formate)

Sources & evidence

ORD record
ord-aebe6c458d3745b2b4c199d98bc7146a
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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