Diisopropylethylamine → Tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)(methyl)carbamate

HRID 1482715Notes

Reaction equation

HRID 1482715 reaction equation
[C:1]([O:5][C:6](=[O:16])[N:7]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([NH2:15])[CH:10]=1)[CH3:8])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[N:23]=[C:22](Cl)[C:21]([F:25])=[CH:20][N:19]=1.CCN(C(C)C)C(C)C.CCCCCC.C(OCC)(=O)C>C(O)CCC.O>[Cl:17][C:18]1[N:23]=[C:22]([NH:15][C:11]2[CH:10]=[C:9]([N:7]([CH3:8])[C:6](=[O:16])[O:5][C:1]([CH3:4])([CH3:2])[CH3:3])[CH:14]=[CH:13][CH:12]=2)[C:21]([F:25])=[CH:20][N:19]=1

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 2507052,4-Dichloro-5-fluoropyrimidineHCID 11492276tert-butyl N-(3-aminophenyl)-N-methylcarbamateHCID 21226206Ethyl acetate hexane

Product 1

HCID 86724363Tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)(methyl)carbamateYield 60.8%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

In a pressure tube tert-butyl(3-aminophenyl)(methyl)carbamate (2.0 g), 2,4-dichloro-5-fluoropyrimidine (2.25 g) and DIPEA (2.32 g) were added in 1-butanol (15 ml). The reaction mixture was heated at 120° C. for 3 hr. The reaction was monitored on TLC using hexane:ethyl acetate (7:3) as mobile phase. The reaction was complete after 3 hr. After completion of the reaction, the reaction mixture was allowed to cool at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate (3×25 ml). Ethyl acetate layer washed with brine solution, dried over sodium sulfate and concentrated under reduced pressure at 40° C. Crude material was purified by using Combiflash chromatography. Product was eluted with 14.8% ethyl acetate in hexane to give 1.93 g of tert-butyl (3-((2-chloro-5-fluoropyrimidin-4-yl)amino)phenyl)(methyl)carbamate. M+1=466.8.

Workup

  1. customAfter completion of the reaction
  2. temperatureto cool at room temperature
  3. extractionextracted with ethyl acetate (3×25 ml)
  4. washEthyl acetate layer washed with brine solution
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure at 40° C
  7. customCrude material was purified
  8. washProduct was eluted with 14.8% ethyl acetate in hexane

Sources & evidence

ORD record
ord-f66136e55ec947daa1b0576b61ab0512
Source dataset
uspto-grants-2016_08
Patent number
US09415049B2

Reaction notes

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