Hydrochloric Acid → 2-Methoxy-1-(4-(3-(4-(5-methylpyridin-2-ylamino)phenoxy)pyrazin-2-YL)piperidin-1-YL)ethanone

HRID 473714Notes

Reaction equation

HRID 473714 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[CH:34]=[CH:33][C:12]([O:13][C:14]3[C:15]([CH:20]4[CH2:25][CH2:24][N:23]([C:26](OC(C)(C)C)=[O:27])[CH2:22][CH2:21]4)=[N:16][CH:17]=[CH:18][N:19]=3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.Cl.C(N(C(C)C)CC)(C)C.[CH3:45][O:46][CH2:47]C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>C(Cl)Cl.O1CCOCC1.O>[CH3:45][O:46][CH2:47][C:26]([N:23]1[CH2:22][CH2:21][CH:20]([C:15]2[C:14]([O:13][C:12]3[CH:11]=[CH:10][C:9]([NH:8][C:5]4[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=4)=[CH:34][CH:33]=3)=[N:19][CH:18]=[CH:17][N:16]=2)[CH2:25][CH2:24]1)=[O:27]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 12251Methoxyacetic AcidHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 59373921Tert-butyl 4-(3-(4-(5-methylpyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

Product 1

HCID 593742462-Methoxy-1-(4-(3-(4-(5-methylpyridin-2-ylamino)phenoxy)pyrazin-2-YL)piperidin-1-YL)ethanone

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of tert-butyl 4-(3-(4-(5-methylpyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate (0.220 g, 0.434 mmol) in DCM (5 mL) was added 4M HCl in dioxane (2 mL). After stirring for 2 h at RT, diisopropylethylamine (0.525 mL, 3.01 mmol), 2-methoxyacetic acid (0.077 mL, 1.004 mmol), and HATU (0.305 g, 0.803 mmol) was added and the reaction mixture was stirred at RT in 2 h. Water was added and the mixture was extracted with DCM (3×), dried over Na2SO4, concentrated. The crude material was purified by reverse phase HPLC, then neutralized with saturated NaHCO3, extracted with DCM (3×), dried over Na2SO4, concentrated to give the title compound. MS (ESI, pos. ion) m/z: 434.2 (M+1). IC50 (uM) 0.000058.

Workup

  1. stirringthe reaction mixture was stirred at RT in 2 h
  2. extractionthe mixture was extracted with DCM (3×)
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customThe crude material was purified by reverse phase HPLC
  6. extractionextracted with DCM (3×)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated

Sources & evidence

ORD record
ord-faf8e295bf664ea2b982f9469b966620
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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