Sodium Carbonate → 6-(5-Chloro-2-fluoropyridin-3-yl)-2-methylpyrimidin-4-amine

HRID 1621974노트

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HRID 1621974 반응식
Cl[C:2]1[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=1.[Cl:10][C:11]1[CH:12]=[C:13](B(O)O)[C:14]([F:17])=[N:15][CH:16]=1.C([O-])(=O)C.[K+].C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.CCO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:10][C:11]1[CH:12]=[C:13]([C:2]2[N:7]=[C:6]([CH3:8])[N:5]=[C:4]([NH2:9])[CH:3]=2)[C:14]([F:17])=[N:15][CH:16]=1

참가 물질

9

반응물 4

HCID 10340Sodium CarbonateHCID 2867546-Chloro-2-methylpyrimidin-4-amineHCID 517044Potassium AcetateHCID 249017795-Chloro-2-fluoropyridine-3-boronic Acid2회

생성물 1

HCID 666002626-(5-Chloro-2-fluoropyridin-3-yl)-2-methylpyrimidin-4-amine수율 69%

시약·촉매·용매 4

HCID 178418397HCID 178418397, 화합물촉매HCID 702Ethanol용매HCID 962Water용매HCID 312751,4-Dioxane용매

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온도
105 °C

실험 절차

A mixture of 6-chloro-2-methylpyrimidin-4-amine (1.03 g, 7.17 mmol) (SynChem Inc,), 5-chloro-2-fluoropyridin-3-ylboronic acid (1.572 g, 8.97 mmol) (Combi-Blocks Inc.), PdCl2AmPhos (0.254 g, 0.359 mmol) and potassium acetate (2.11 g, 21.52 mmol) in 8 mL of dioxane, 1 mL of EtOH and 4 mL of water in a sealed glass tube was heated in a microwave at 105° C. for 45 min. Crude liquid chromatography/mass spectropscopy indicated the reaction was not completed. To the reaction mixture was added 83 mg of Pd(PPh3)4, 300 mg of 5-chloro-2-fluoropyridin-3-ylboronic acid and 0.3 mL of 2N Na2CO3. It was heated in a microwave at 115° C. for 20 min. The precipitated yellow solid was filtered, washed with 3 mL of 1 N NaOH, followed by 3 mL of water and 5 mL of EtOAc. The yellow crystalline solid was dried in a vacuum oven at 45° C. for 18 h to provide 6-(5-chloro-2-fluoropyridin-3-yl)-2-methylpyrimidin-4-amine (1.18 g, 68% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.59 (dd, J=8.4, 2.7 Hz, 1H), 8.40 (m, 1H), 7.08 (br, 2H), 6.82 (d, J=1.8Hz, 1H), 2.40 (s, 3H). m/z (ESI, positive ion) 238.9 (M+H)+.

후처리

  1. temperatureIt was heated in a microwave at 115° C. for 20 min
  2. filtrationThe precipitated yellow solid was filtered
  3. washwashed with 3 mL of 1 N NaOH
  4. customThe yellow crystalline solid was dried in a vacuum oven at 45° C. for 18 h

출처 및 근거

ORD 기록
ord-9bab07771d0a4b33817b436f68893250
출처 데이터셋
uspto-grants-2014_07
특허 번호
US08772480B2

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