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

HRID 1482693Notes

Reaction equation

HRID 1482693 reaction equation
[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:22]=[C:23]([NH:27][C:28](=[O:35])[CH2:29][C:30](OCC)=[O:31])[CH:24]=[CH:25][CH:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:7]=1.N#N.[Li+].[Br-].[BH4-].[Na+]>C1COCC1.O.C(OCC)(=O)C.CCCCCC>[F:1][C:2]1[C:3]([NH:20][C:21]2[CH:22]=[C:23]([NH:27][C:28](=[O:35])[CH2:29][CH2:30][OH:31])[CH:24]=[CH:25][CH:26]=2)=[N:4][C:5]([NH:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH2:16][CH2:17][O:18][CH3:19])=[CH:11][CH:10]=2)=[N:6][CH:7]=1

Participants

8

Reactant 4

HCID 947NitrogenHCID 82050Lithium BromideHCID 4311764Sodium borohydrideHCID 86724347Ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate

Product 1

HCID 86724348N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-3-hydroxypropanamide

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

To a solution of ethyl 3-((3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)amino)-3-oxopropanoate (0.17 g) in THF (5 mL), in a 25 mL 3-necked RBF equipped with N2 bubbler, were added LiBr (0.182 g) and NaBH4 (0.081 g). The reaction mixture was stirred at reflux temperature for 3 hr. The reaction was monitored on TLC using ethyl acetate:hexane (8:2) as mobile phase. After completion, the reaction mixture was poured into water. The product was extracted with ethyl acetate and the organic layer was washed with brine and concentrated completely under reduce pressure at 40° C. The obtained solid was purified by column chromatography. Product was eluted with 100% ethyl acetate to give, after concentration, 10.2 mg of N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-3-hydroxypropanamide. 1H NMR: DMSO-d6 (400 MHz): 2.50 (s, 2H), 3.30 (s, 3H), 3.63 (t, 2H, J=4.4), 3.70 (t, 2H, J=5.2), 4.01 (t, 2H, J=4), 4.67 (t, 1H, J=5.2), 6.79 (m, 2H), 7.24 (t, 1H, J=8), 7.33 (d, 1H, J=7.6), 7.51 (m, 3H), 7.85 (s, 1H), 8.05 (d, 1H, J=3.6), 8.94 (s, 1H), 9.34 (s, 1H), 9.87 (s, 1H).

Workup

  1. temperatureat reflux temperature for 3 hr
  2. extractionThe product was extracted with ethyl acetate
  3. washthe organic layer was washed with brine
  4. concentrationconcentrated completely
  5. customat 40° C
  6. customThe obtained solid was purified by column chromatography
  7. washProduct was eluted with 100% ethyl acetate
  8. customto give
  9. concentrationafter concentration, 10.2 mg of N-(3-((5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)amino)phenyl)-3-hydroxypropanamide

Sources & evidence

ORD record
ord-439a63d8dfc948a89464e9e21c837b5f
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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