2-Aminopyrimidine → 2,6-dichloro-N-(2-(pyrimidin-2-ylamino)pyridin-4-yl)benzamide

HRID 449878노트

반응식

HRID 449878 반응식
Br[C:2]1[CH:7]=[C:6]([NH:8][C:9](=[O:18])[C:10]2[C:15]([Cl:16])=[CH:14][CH:13]=[CH:12][C:11]=2[Cl:17])[CH:5]=[CH:4][N:3]=1.[NH2:19][C:20]1[N:25]=[CH:24][CH:23]=[CH:22][N:21]=1.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.C([O-])([O-])=O.[Cs+].[Cs+]>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].O1CCOCC1>[Cl:17][C:11]1[CH:12]=[CH:13][CH:14]=[C:15]([Cl:16])[C:10]=1[C:9]([NH:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH:19][C:20]2[N:25]=[CH:24][CH:23]=[CH:22][N:21]=2)[CH:7]=1)=[O:18]

참가 물질

7

반응물 4

HCID 79782-AminopyrimidineHCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 75464886N-(2-Bromopyridin-4-yl)-2,6-dichlorobenzamide

생성물 1

HCID 596180362,6-dichloro-N-(2-(pyrimidin-2-ylamino)pyridin-4-yl)benzamide수율 12%

시약·촉매·용매 2

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 312751,4-Dioxane용매

실험 절차

To a microwave tube were added N-(2-bromopyridin-4-yl)-2,6-dichlorobenzamide (0.120 g, 0.347 mmol), 2-aminopyrimidine (0.040 g, 0.42 mmol), Pd2(dba)3 (0.030 g, 0.035 mmol), XantPhos (0.040 g, 0.070 mmol), Cs2CO3 (0.23 g, 0.70 mmol) and dioxane (2 mL). The mixture was degassed with N2 for 5 min. The resulting mixture was irradiated in a microwave reactor at 140° C. for 50 min and then cooled to room temperature. The mixture was filtered through Celite and concentrated under reduced pressure. The residue was dissolved in DMF and purified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min) to give the desired product as a white solid (15 mg, 12% yield). 1H NMR (500 MHz, MeOH-d4): δ 8.72 (s, 1H), 8.56 (d, J=4.5 Hz, 2H), 8.21 (d, J=5.5 Hz, 2H), 7.53-7.45 (m, 4H), 6.95 (t, J=5.0 Hz, 1H). LCMS (ESI) m/z: 360.0 [M+H+].

후처리

  1. customThe mixture was degassed with N2 for 5 min
  2. customThe resulting mixture was irradiated in a microwave reactor at 140° C. for 50 min
  3. filtrationThe mixture was filtered through Celite
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved in DMF
  6. custompurified by prep-HPLC (Gilson GX 281, Shim-pack PRC-ODS 250 mm×20 mm×2, gradient: CH3CN/10 mm/L NH4HCO3, 17 min)

출처 및 근거

ORD 기록
ord-c90d055e638c406c83bb5bb204129c3f
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486950B2

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