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

HRID 449878ノート

反応式

HRID 449878 の反応式
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]

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 312751,4-Dioxane溶媒

実験手順

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+].

後処理

  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)

出典と根拠

ORDレコード
ord-c90d055e638c406c83bb5bb204129c3f
出典データセット
uspto-grants-2013_07
特許番号
US08486950B2

反応ノート

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