N,N-Dimethylethylenediamine → HCID 70976561, compound

HRID 882285Notes

Reaction equation

HRID 882285 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][N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:30])(=[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.[CH3:64][N:65]([CH3:69])[CH2:66][CH2:67][NH2:68]>CN(C=O)C>[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]([NH:68][CH2:67][CH2:66][N:65]([CH3:69])[CH3:64])=[O:19])=[CH:16][N:15]=3)=[CH:11][CH:12]=2)[C@H:7]([NH:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][N:25]=2)[CH2:6][C@@H:5]1[CH3:30])(=[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 70976697HCID 70976697, compound

Product 1

HCID 70976561HCID 70976561, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a flask charged with 6-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)nicotinic acid (for a preparation see Intermediate 28)(50 mg, 0.124 mmol) and HATU (56.7 mg, 0.149 mmol) was added DMF (2 mL) and the resulting mixture was treated with DIPEA (0.065 mL, 0.373 mmol) then after 5 min with N1,N1-dimethylethane-1,2-diamine (21.90 mg, 0.248 mmol. The resulting solution was stirred at room temperature for 30 min then partitioned between EtOAc and saturated NaHCO3. The organic phase was separated and aqueous layer extracted with EtOAc (×2). The combined organic layers were washed with saturated NaHCO3, dried over MgSO4 and concentrated in vacuo. The residue divided into 2 portions and each was purified by MDAP (HpH). The appropriate fractions were collected and concentrated in vacuo. The residue was dissolved in MeOH and concentrated again, then co-evaporated with toluene. The residue were then dissolved in 1,4-dioxane (2 mL) and treated with hydrogen chloride in 1,4-dioxane (4N, 0.5 mL). After 2 min the solvent was evaporated in vacuo and the precipitate formed triturated with Et2O then dried under house vacuum to give 6-((2S,4R)-1-acetyl-2-methyl-4-(pyridin-2-ylamino)-1,2,3,4-tetrahydroquinolin-6-yl)-N-(2-(dimethylamino)ethyl)nicotinamide, as the d-hydrochloride salt (37 mg, 0.068 mmol, 54.6% yield) as a yellow solid. LCMS (HpH, 2 min), Rt=0.81 min, MH+=473.

Workup

  1. customthen partitioned between EtOAc and saturated NaHCO3
  2. customThe organic phase was separated
  3. extractionaqueous layer extracted with EtOAc (×2)
  4. washThe combined organic layers were washed with saturated NaHCO3
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customeach was purified by MDAP (HpH)
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated in vacuo
  10. dissolutionThe residue was dissolved in MeOH
  11. concentrationconcentrated again
  12. dissolutionThe residue were then dissolved in 1,4-dioxane (2 mL)
  13. additiontreated with hydrogen chloride in 1,4-dioxane (4N, 0.5 mL)
  14. customAfter 2 min the solvent was evaporated in vacuo
  15. customthe precipitate formed
  16. customtriturated with Et2O
  17. customthen dried under house vacuum

Sources & evidence

ORD record
ord-1703c118f0314b80a643faaae6574806
Source dataset
uspto-grants-2015_03
Patent number
US08993554B2

Reaction notes

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