Serinol → HCID 71469145, compound

HRID 882269Notes

Reaction equation

HRID 882269 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]([OH:23])=O)=[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].[NH2:35][CH:36]([CH2:39][OH:40])[CH2:37][OH:38].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:35][CH:36]([CH2:39][OH:40])[CH2:37][OH:38])=[O:23])=[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 68294SerinolHCID 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 71469145HCID 71469145, compoundYield 42%

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)(169 mg, 0.384 mmol) and 2-aminopropane-1,3-diol (69.9 mg, 0.767 mmol) in DMF (2 ml) were added HATU (190 mg, 0.499 mmol) and DIPEA (0.201 mL, 1.151 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-(1,3-dihydroxypropan-2-yl)acetamide (83 mg, 42%) as a colourless oil. LCMS (Formate, 2 min), Rt=0.73 min, MH+=514.

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-97b7d53c7d904a45b2747a3170b7b2b8
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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