5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine → N-(5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide

HRID 2278981Notes

Reaction equation

HRID 2278981 reaction equation
[O:1]=[C:2]1[N:6]([CH:7]2[CH2:12][CH2:11][O:10][CH2:9][CH2:8]2)[CH2:5][CH2:4][N:3]1[C:13](Cl)=[O:14].[CH3:16][N:17]1[CH:21]=[C:20]([C:22]2[N:27]=[CH:26][N:25]=[C:24]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH2:35])=[N:33][CH:34]=3)[CH:23]=2)[CH:19]=[N:18]1>C(Cl)Cl>[CH3:16][N:17]1[CH:21]=[C:20]([C:22]2[N:27]=[CH:26][N:25]=[C:24]([O:28][C:29]3[CH:30]=[CH:31][C:32]([NH:35][C:13]([N:3]4[CH2:4][CH2:5][N:6]([CH:7]5[CH2:12][CH2:11][O:10][CH2:9][CH2:8]5)[C:2]4=[O:1])=[O:14])=[N:33][CH:34]=3)[CH:23]=2)[CH:19]=[N:18]1

Participants

4

Reactant 2

HCID 904033665-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amineHCID 904274552-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carbonyl chloride

Product 1

HCID 86270215N-(5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamideYield 67%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A 0° C. solution of Example B2 (0.14 g, 0.60 mmol) in DCM (3 mL) was treated drop-wise with a solution of 5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-amine (0.08 g, 0.30 mmol) and TEA (0.1 mL, 0.9 mmol) in DCM (2 mL), warmed to RT and stirred for 2 h. The mixture was concentrated to dryness, purified via silica gel chromatography (MeOH/DCM), treated with Et2O and the resulting solid collected via filtration to afford N-(5-((6-(1-methyl-1H-pyrazol-4-yl)pyrimidin-4-yl)oxy)pyridin-2-yl)-2-oxo-3-(tetrahydro-2H-pyran-4-yl)imidazolidine-1-carboxamide (93 mg, 67%). 1H NMR (400 MHz, DMSO-d6): δ 10.94 (s, 1 H), 8.62 (d, J=1.1 Hz, 1 H), 8.46 (s, 1 H), 8.22 (m, 1 H), 8.16 (d, J=0.7 Hz, 1 H), 8.04 (d, J=9.0 Hz, 1 H), 7.74 (dd, J=9.0, 2.9 Hz, 1 H), 7.42 (d, J=1.1 Hz, 1 H), 3.89 (s, 3 H), 4.00-3.70 (m, 5 H), 3.42-3.39 (m, 4 H), 1.76-1.65 (m, 2 H), 1.59 (m, 2 H); MS (ESI) m/z: 465.2 (M+H+).

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. custompurified via silica gel chromatography (MeOH/DCM)
  3. additiontreated with Et2O
  4. filtrationthe resulting solid collected via filtration

Sources & evidence

ORD record
ord-b07d508309b44af9954c32107ea0e950
Source dataset
uspto-grants-2015_09
Patent number
US09133183B2

Reaction notes

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