Water → HCID 86724361, compound

HRID 1482708Notes

Reaction equation

HRID 1482708 reaction equation
Cl[C:2]1[N:7]=[C:6]([N:8]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N:22]([OH:27])[C:23](=[O:26])[CH:24]=[CH2:25])[CH:17]=2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:5]([F:28])=[CH:4][N:3]=1.[CH3:29][O:30][CH2:31][CH2:32][O:33][C:34]1[CH:40]=[CH:39][C:37]([NH2:38])=[CH:36][CH:35]=1.CCCCCC.C(OCC)(=O)C.O>O1CCOCC1>[F:28][C:5]1[C:6]([N:8]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([N:22]([OH:27])[C:23](=[O:26])[CH:24]=[CH2:25])[CH:17]=2)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[N:7][C:2]([NH:38][C:37]2[CH:36]=[CH:35][C:34]([O:33][CH2:32][CH2:31][O:30][CH3:29])=[CH:40][CH:39]=2)=[N:3][CH:4]=1

Participants

6

Reactant 4

HCID 962WaterHCID 38798854-(2-Methoxyethoxy)anilineHCID 21226206Ethyl acetate hexaneHCID 86724360HCID 86724360, compound

Product 1

HCID 86724361HCID 86724361, compoundYield 75.8%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

In a 25 mL three neck RBF with thermometer pocket, a solution of tert-butyl (2-chloro-5-fluoropyrimidin-4-yl)(3-(N-hydroxyacrylamido)phenyl)carbamate (0.250 g) in 1,4-dioxane (8.0 mL) was added. 4-(2-Methoxyethoxy)aniline (0.122 g) was added and the reaction was degassed for 10 minutes under argon. After 10 minutes, Xantphose (0.0176 g) and Cs2CO3 (0.396 g) were added and again degassed the reaction for 10 minutes followed by addition of Pd (OAc)2 (0.003 g) under argon. The reaction was heated to 80° C. and stirred for 3.5 hr under argon. The reaction was monitored on TLC using hexane:ethyl acetate (2:8) as mobile phase. After completion of the reaction, the reaction mixture was allowed to cool at room temperature. The reaction mixture was poured into water and product was extracted with ethyl acetate (3×25 ml). Ethyl acetate layer washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure to give 0.250 g of tert-butyl (5-fluoro-2-((4-(2-methoxyethoxy)phenyl)amino)pyrimidin-4-yl)(3-(N-hydroxyacrylamido)phenyl)carbamate. This crude material was used in the next step without any further purification. M+1=539.9.

Workup

  1. customthe reaction was degassed for 10 minutes under argon
  2. additionXantphose (0.0176 g) and Cs2CO3 (0.396 g) were added
  3. customagain degassed
  4. customthe reaction for 10 minutes
  5. customAfter completion of the reaction
  6. temperatureto cool at room temperature
  7. extractionwas extracted with ethyl acetate (3×25 ml)
  8. washEthyl acetate layer washed with brine solution
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-0295e331a5ef4c2eb56e9a81391e94bb
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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