Cesium carbonate → N-(2-methyl-5-nitropyridin-3-yl)-4-(pyridin-3-yl)pyrimidin-2-amine

HRID 2174641

반응식

HRID 2174641 반응식
Br[C:2]1[C:3]([CH3:11])=[N:4][CH:5]=[C:6]([N+:8]([O-:10])=[O:9])[CH:7]=1.[N:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]2[CH:23]=[CH:22][N:21]=[C:20]([NH2:24])[N:19]=2)[CH:13]=1.C([O-])([O-])=O.[Cs+].[Cs+].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH3:11][C:3]1[C:2]([NH:24][C:20]2[N:19]=[C:18]([C:14]3[CH:13]=[N:12][CH:17]=[CH:16][CH:15]=3)[CH:23]=[CH:22][N:21]=2)=[CH:7][C:6]([N+:8]([O-:10])=[O:9])=[CH:5][N:4]=1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 124505824-(Pyridin-3-yl)pyrimidin-2-amineHCID 184588223-Bromo-2-methyl-5-nitropyridine

생성물 1

HCID 46910559N-(2-methyl-5-nitropyridin-3-yl)-4-(pyridin-3-yl)pyrimidin-2-amine수율 50.3%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 1140Toluene용매

반응 조건

온도
90 °C

실험 절차

To a mixture of 3-bromo-2-methyl-5-nitro-pyridine (380 mg, 1.75 mmol) and 4-pyridin-3-yl-pyrimidin-2-ylamine (250 mg, 1.45 mmol) in dry toluene (20 mL) were added Cs2CO3 (710 mg, 2.18 mmol), Pd2(dba)3 (26 mg, 0.028 mmol) and Xantphos (50 mg, 0.086 mmol). The mixture was evacuated and purged with N2 (3 cycles), heated to 90° C. under N2 for 16 h. After completion (monitored by TLC), the reaction mixture was cooled to rt, diluted with EtOAc and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (SiO2) using CH2Cl2-MeOH (98:2) to afford product (225 mg, 50%). 1H NMR (200 MHz, CDCl3): δ 2.76 (s, 3H), 7.23 (m, 1H), 7.38 (d, J=6.0 Hz, 1H), 7.51 (m, 1H), 8.51 (m, 1H), 8.63 (d, J=6.0 Hz, 1H), 8.77 (m, 1H), 9.04 (d, J=2.0 Hz, 1H), 9.28 (d, J=2.0 Hz, 1H), 9.77 (d, J=2.0 Hz, 1H); Mass [M+H]+: 309.

후처리

  1. customThe mixture was evacuated
  2. custompurged with N2 (3 cycles)
  3. temperatureAfter completion (monitored by TLC), the reaction mixture was cooled to rt
  4. additiondiluted with EtOAc
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe residue was purified by column chromatography (SiO2)

출처 및 근거

ORD 기록
ord-4939f1cea86c47cf8234de3723e13c1a
출처 데이터셋
uspto-grants-2015_06
특허 번호
US09062023B2

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