Sodium Carbonate → 5-(4-Chloro-2-fluorophenyl)pyrimidin-2-amine

HRID 1523771노트

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HRID 1523771 반응식
Br[C:2]1[CH:3]=[N:4][C:5]([NH2:8])=[N:6][CH:7]=1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[C:12]([F:19])[CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+]>FC(F)(F)C([O-])=O.[Pd+2].FC(F)(F)C([O-])=O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:2]2[CH:3]=[N:4][C:5]([NH2:8])=[N:6][CH:7]=2)=[C:12]([F:19])[CH:11]=1

참가 물질

7

반응물 3

HCID 10340Sodium CarbonateHCID 2313102-Amino-5-bromopyrimidineHCID 4193595(4-Chloro-2-fluorophenyl)boronic acid

생성물 1

HCID 790224125-(4-Chloro-2-fluorophenyl)pyrimidin-2-amine수율 74%

시약·촉매·용매 3

HCID 11776Triphenylphosphine촉매HCID 2733347Palladium(II) trifluoroacetate촉매HCID 962Water용매

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온도
50 °C

실험 절차

To a 500 mL round-bottomed flask were added 5-bromo-2-aminopyrimidine (4.0 g, 23 mmol), 4-chloro-2-fluorophenylboronic acid (3.9 g, 23 mmol), palladium(II)trifluoroacetate (240 mg, 0.72 mmol), and triphenylphoshine (373 mg, 1.40 mmol). The reaction vessel was fitted with a rubber septum, sparged with nitrogen and then charged with sparged toluene (75 mL), ethanol (75 mL), and a 2M solution of sodium carbonate (42 mL, 84 mmol) (solvents were sparged individually nitrogen gas for 30 minutes). The resulting mixture was stirred vigorously and heated at 50° Celsius. After 12 hours, the mixture was cooled to rt and treated with 100 mL of water. The precipitate was isolated via vacuum filtration, and the filtrate extracted with EtOAC. The EtOAc solution was dried, filtered and concentrated to dryness. The resultant solids were recrystallized from IPA (80 mL) to afford title compound (3.8 g, 74%). MS (ESI): mass calcd. for C10H7ClFN3, 223.03; m/z found, 224.0 [M+H]+. 1H NMR (500 MHz, DMSO-d6) δ 8.44 (d, J=1.4, 2H), 7.59 (m, 1H), 7.54 (dd, J=10.7, 2.1, 1H), 7.37 (dd, J=8.3, 2.1, 1H), 6.94 (s, 2H).

후처리

  1. customThe reaction vessel was fitted with a rubber septum
  2. customsparged with nitrogen
  3. additioncharged with sparged toluene (75 mL), ethanol (75 mL)
  4. temperaturethe mixture was cooled to rt
  5. customThe precipitate was isolated via vacuum filtration
  6. extractionthe filtrate extracted with EtOAC
  7. dry with materialThe EtOAc solution was dried
  8. filtrationfiltered
  9. concentrationconcentrated to dryness
  10. customThe resultant solids were recrystallized from IPA (80 mL)

출처 및 근거

ORD 기록
ord-ec10fda641864c96b7265cbcc79d29e7
출처 데이터셋
uspto-grants-2015_07
특허 번호
US09079866B2

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