O-Phenylenediamine → N-[9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purin-2-yl]benzene-1,2-diamine

HRID 1945635ノート

反応式

HRID 1945635 の反応式
Cl[C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:12][N:13]3[CH2:18][CH2:17][CH:16]([CH:19]4[CH2:22][O:21][CH2:20]4)[CH2:15][CH2:14]3)[N:8]2[CH3:11])=[C:4]([N:23]2[CH2:28][CH2:27][O:26][CH2:25][CH2:24]2)[N:3]=1.[C:29]1([NH2:36])[C:30]([NH2:35])=[CH:31][CH:32]=[CH:33][CH:34]=1.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.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][N:8]1[C:7]([CH2:12][N:13]2[CH2:14][CH2:15][CH:16]([CH:19]3[CH2:20][O:21][CH2:22]3)[CH2:17][CH2:18]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([NH:35][C:30]1[C:29]([NH2:36])=[CH:34][CH:33]=[CH:32][CH:31]=1)=[N:3][C:4]=2[N:23]1[CH2:28][CH2:27][O:26][CH2:25][CH2:24]1

参加物

7

反応物 4

HCID 7243O-PhenylenediamineHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 596054062-Chloro-9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purine

生成物 1

HCID 59605317N-[9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-ylpiperidin-1-ylmethyl)-9H-purin-2-yl]benzene-1,2-diamine収率 50%

試薬・触媒・溶媒 2

HCID 9811564Bis(dibenzylideneacetone)palladium触媒HCID 6228Dimethylformamide溶媒

実験手順

A mixture of 2-chloro-9-methyl-6-morpholin-4-yl-8-(4-oxetan-3-yl-piperidin-1-ylmethyl)-9H-purine (0.2 g, 0.49 mmol), benzene-1,2-diamine (0.106 g, 0.98 mmol), Xphos (0.047 g, 0.098 mmol), Pd2(dba)3 (0.022 g, 0.025 mmol) and Cs2CO3 (0.32 g, 0.98 mmol) in DMF (2 mL) was subjected to microwave irradiation at 150° C. for 30 min. The suspension was filtered through Celite and the solution was concentrated in vacuo. The residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90) to give N-[9-Methyl-6-morpholin-4-yl-8-(4-oxetan-3-yl-piperidin-1-ylmethyl)-9H-purin-2-yl]benzene-1,2-diamine as yellow foam (0.117 g, 50%). LCMS (Method A): RT=2.14 min, [M+H]+ 479.2

後処理

  1. customirradiation at 150° C. for 30 min
  2. filtrationThe suspension was filtered through Celite
  3. concentrationthe solution was concentrated in vacuo
  4. customThe residue was purified by flash chromatography (Si—PPC, MeOH:DCM, gradient 0:100 to 10:90)

出典と根拠

ORDレコード
ord-71c0ae989f3843fcb3e7052c8d75477d
出典データセット
uspto-grants-2013_03
特許番号
US08394796B2

反応ノート

読み込み中…