Cesium carbonate → 2-[2-(2,5-Dimethyl-2H-pyrazol-3-ylamino)-5-isopropenyl-pyridin-4-ylamino]-N-methyl-benzamide

HRID 1472563노트

반응식

HRID 1472563 반응식
Cl[C:2]1[CH:7]=[C:6]([NH:8][C:9]2[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=2[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([CH3:21])=[CH2:20])=[CH:4][N:3]=1.[CH3:22][N:23]1[C:27]([NH2:28])=[CH:26][C:25]([CH3:29])=[N:24]1.C([O-])([O-])=O.[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1>CC([O-])=O.CC([O-])=O.[Pd+2].O1CCOCC1>[CH3:22][N:23]1[C:27]([NH:28][C:2]2[CH:7]=[C:6]([NH:8][C:9]3[CH:18]=[CH:17][CH:16]=[CH:15][C:10]=3[C:11]([NH:13][CH3:14])=[O:12])[C:5]([C:19]([CH3:21])=[CH2:20])=[CH:4][N:3]=2)=[CH:26][C:25]([CH3:29])=[N:24]1

참가 물질

7

반응물 4

HCID 10796Cesium carbonateHCID 5207211,3-Dimethyl-1H-pyrazol-5-amineHCID 634876Binap, (A+-)-HCID 575169072-(2-Chloro-5-isopropenyl-pyridin-4-ylamino)-N-methyl-benzamide

생성물 1

HCID 462152722-[2-(2,5-Dimethyl-2H-pyrazol-3-ylamino)-5-isopropenyl-pyridin-4-ylamino]-N-methyl-benzamide

시약·촉매·용매 2

HCID 167845palladium(II) acetate촉매HCID 312751,4-Dioxane용매

실험 절차

To a 10 mL microwave tube was added 2-(2-chloro-5-isopropenyl-pyridin-4-ylamino)-N-methyl-benzamide (0.075 g, 0.25 mmol, 1 eq), 2,5-dimethyl-2H-pyrazol-3-ylamine (0.055 g, 0.50 mmol, 2 eq), Cs2CO3 (0.24 g, 0.74 mmol, 3 eq) and 1,4-dioxane (3 mL). The resulting mixture was degassed with N2 for 30 minutes. Then Pd(OAc)2 (0.015 g, 0.07 mmol, 0.27 eq) and BINAP (0.046 g, 0.074 mmol, 0.3 eq) were added and the mixture degassed again with N2 for another 10 minutes. The resulting reaction mixture was irradiated in a CEM microwave at 110° C. and 150 W for 45 min. The progress of the reaction was monitored by LCMS. After it was complete, Cs2CO3 was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting crude product was purified by column chromatography over neutral alumina using 0.2% MeOH-DCM as the eluant. This gave the title compound as an off white solid (180 mg, 48%). 1H-NMR (400 MHz, DMSO-d6): δ 2.02-2.10 (m, 6H), 2.73-2.74 (d, 3H, J=4.48 Hz), 3.53 (s, 3H), 5.05 (s, 1H), 5.31 (s, 1H), 5.97 (s, 1H), 6.67 (s, 1H), 6.90-7.05 (m, 1H), 7.4-7.55 (m, 2H), 7.61-7.63 (d, 1H, J=7.04 Hz), 7.76 (s, 1H), 8.48 (s, 1H), 8.54-8.67 (brs, 1H), 9.61 (s, 1H). LC-MS [M+H]+=377.4.

후처리

  1. customThe resulting mixture was degassed with N2 for 30 minutes
  2. customthe mixture degassed again with N2 for another 10 minutes
  3. customThe resulting reaction mixture
  4. customwas irradiated in a CEM microwave at 110° C.
  5. customCs2CO3 was removed by filtration
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe resulting crude product was purified by column chromatography over neutral alumina using 0.2% MeOH-DCM as the eluant

출처 및 근거

ORD 기록
ord-4009e1a88ac84cf39f961ef4a739b74a
출처 데이터셋
uspto-grants-2015_04
특허 번호
US09012479B2

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