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

HRID 1482693노트

반응식

HRID 1482693 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 21226206Ethyl acetate hexane용매

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-439a63d8dfc948a89464e9e21c837b5f
출처 데이터셋
uspto-grants-2016_08
특허 번호
US09415049B2

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