2-Amino-4-methylpyrimidine → 2,6-dichloro-N-(2-(4-methylpyrimidin-2-ylamino)pyridin-4-yl)benzamide

HRID 449879

반응식

HRID 449879 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]=[C:24]([CH3:26])[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]=[C:24]([CH3:26])[CH:23]=[CH:22][N:21]=2)[CH:7]=1)=[O:18]

참가 물질

7

반응물 4

HCID 79392-Amino-4-methylpyrimidineHCID 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 596180282,6-dichloro-N-(2-(4-methylpyrimidin-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 (0.15 g, 0.43 mmol), 2-amino-4-methylpyrimidine (0.056 g, 0.52 mmol), Pd2(dba)3 (0.040 g, 0.043 mmol), XantPhos (0.050 g, 0.087 mmol), Cs2CO3 (0.28 g, 0.87 mmol) and dioxane (2 mL). The mixture was degassed with N2 for 10 min. The resulting mixture was irradiated in a microwave reactor at 140° C. for 3 hours 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 (19 mg, yield: 12%). 1H NMR (500 MHz, MeOH-d4): δ 8.88 (s, 1H), 8.36 (d, J=5.5 Hz, 1H), 8.16 (d, J=6.0 Hz, 1H), 7.64 (s, 1H), 7.45-7.38 (m, 4H), 6.85 (d, J=5.5 Hz, 1H), 2.50 (s, 3H). LCMS (ESI) m/z: 374.0 [M+H+].

후처리

  1. customThe mixture was degassed with N2 for 10 min
  2. customThe resulting mixture was irradiated in a microwave reactor at 140° C. for 3 hours
  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-95dd39581c024ef1831c1702d1149b35
출처 데이터셋
uspto-grants-2013_07
특허 번호
US08486950B2

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