Nitrogen → N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)oxirane-2-carboxamide

HRID 2274258Notes

Reaction equation

HRID 2274258 reaction equation
N#N.CS(O[CH2:8][CH:9]([OH:39])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[C:15]([NH:19][C:20]2[C:25]([F:26])=[CH:24][N:23]=[C:22]([NH:27][C:28]3[CH:33]=[CH:32][C:31]([O:34][CH2:35][CH2:36][O:37][CH3:38])=[CH:30][CH:29]=3)[N:21]=2)[CH:14]=1)=[O:11])(=O)=O.C1COCC1.[H-].[Na+]>C(OCC)(=O)C.O.CCCCCC.C(OCC)(=O)C>[F:26][C:25]1[C:20]([NH:19][C:15]2[CH:14]=[C:13]([NH:12][C:10]([CH:9]3[CH2:8][O:39]3)=[O:11])[CH:18]=[CH:17][CH:16]=2)=[N:21][C:22]([NH:27][C:28]2[CH:29]=[CH:30][C:31]([O:34][CH2:35][CH2:36][O:37][CH3:38])=[CH:32][CH:33]=2)=[N:23][CH:24]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 902338843-((3-((5-Fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate

Product 1

HCID 89906279N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)oxirane-2-carboxamideYield 44.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
0 °C

Procedure

Into a 25 mL 3-neck RBF equipped with N2-bubbler and thermo pocket was charged 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-2-hydroxy-3-oxopropyl methanesulfonate (0.03 g) and THF (2.0 mL). The reaction mixture was cooled to 0° C. and NaH (2.2 mg) was added. The reaction mixture was warmed to room temperature and stirred for 45 min. Completion of reaction was monitored on TLC using hexane:ethyl acetate (2:8) as mobile phase. After completion of reaction, the mixture was diluted with ethyl acetate (20 mL) and water was added. The organic layer was dried over sodium sulfate and solvent was removed under reduced pressure. Crude product purified by tituration with diethyl ether to give 0.011 g of N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)oxirane-2-carboxamide. 1H NMR: DMSO-d6 (400 MHz): 2.881 (d, 1H, J=4.4), 2.98 (t, 1H), 3.30 (s, 3H), 3.63 (m, 3H), 4.01 (t, 2H, J=4.0), 6.77 (d, 2H, J=9.2), 7.27 (t, 1H, J=8), 7.35 (d, 1H, J=8.4), 7.52 (d, 3H, J=8.8), 7.93 (s, 1H), 8.07 (d, 1H, J=3.2), 8.99 (s, 1H), 9.37 (d, 1H, J=18), 10.19 (s, 1H).

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. customCompletion of reaction
  3. customAfter completion of reaction
  4. additionwas added
  5. dry with materialThe organic layer was dried over sodium sulfate and solvent
  6. customwas removed under reduced pressure
  7. customCrude product purified by tituration with diethyl ether

Sources & evidence

ORD record
ord-220e38a77d454df1944fd8402c65ebfe
Source dataset
uspto-grants-2015_09
Patent number
US09126950B2

Reaction notes

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