Cesium carbonate → 2-(3-{6-[(2,3-Dihydro-benzofuran-2-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid

HRID 2110782ノート

反応式

HRID 2110782 の反応式
Cl[C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH2:11][CH:12]2[CH2:16][C:15]3[CH:17]=[CH:18][CH:19]=[CH:20][C:14]=3[O:13]2)[CH:3]=1.[C:21]([C:24]([C:27]1[CH:28]=[C:29](B(O)O)[CH:30]=[CH:31][CH:32]=1)([CH3:26])[CH3:25])([OH:23])=[O:22].C([O-])([O-])=O.[Cs+].[Cs+]>COCCOC.O.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[O:13]1[C:14]2[CH:20]=[CH:19][CH:18]=[CH:17][C:15]=2[CH2:16][CH:12]1[CH2:11][NH:10][C:4]1[N:5]=[C:6]([O:8][CH3:9])[N:7]=[C:2]([C:29]2[CH:28]=[C:27]([C:24]([CH3:26])([CH3:25])[C:21]([OH:23])=[O:22])[CH:32]=[CH:31][CH:30]=2)[CH:3]=1

参加物

7

反応物 3

HCID 10796Cesium carbonateHCID 442489972-(3-Boronophenyl)-2-methylpropanoic acidHCID 86615711(6-Chloro-2-methoxy-pyrimidin-4-yl)-(2,3-dihydro-benzofuran-2-ylmethyl)-amine

生成物 1

HCID 576359972-(3-{6-[(2,3-Dihydro-benzofuran-2-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid収率 58.1%

試薬・触媒・溶媒 3

HCID 11979704Tetrakis(triphenylphosphine)palladium触媒HCID 962Water溶媒2 回HCID 80711,2-Dimethoxyethane溶媒

反応条件

温度
85 °C

実験手順

A mixture of (6-chloro-2-methoxy-pyrimidin-4-yl)-(2,3-dihydro-benzofuran-2-ylmethyl)-amine (167 mg, 0.57 mmol), 3-(1-carboxy-1-methyl-ethyl)-phenyl-boronic acid (155 mg, 0.75 mmol), and Cs2CO3 (0.46 g, 1.43 mmol) in ethylene glycol dimethyl ether (8 mL) and water (2 mL) is degassed by bubbling with Ar gas for 5 minutes, and treated with tetrakis(triphenylphosphine) palladium (0) (33 mg, 0.03 mmol) at room temperature. The mixture is heated at 85° C. for 3 h. The mixture is diluted with H2O (20 mL), and extracted with EtOAc (10 mL). The aqueous layer is separated, acidified to pH 2.5 with 1M HCl solution, and extracted with EtOAc (2×10 mL). The extracts are dried (MgSO4), filtered through a short pad of SiO2 to afford 2-(3-{6-[(2,3-dihydro-benzofuran-2-ylmethyl)-amino]-2-methoxy-pyrimidin-4-yl}-phenyl)-2-methyl-propionic acid (139 mg, Example 90). LCMS: RT=2.05 minutes; MS: 420 (M+H); 1H NMR (300 MHz, DMSO-d6) □12.4 (1H, s), 8.05-7.8 (2H, m), 7.5-7.1 (5H, m), 6.8-6.75 (2H, m), 5 (1H, s), 4 (3H, brs), 3.65 (2H, brs), 3.4-2.95 (2H, m), 1.48 (6H, s).

後処理

  1. customis degassed
  2. customby bubbling with Ar gas for 5 minutes
  3. extractionextracted with EtOAc (10 mL)
  4. customThe aqueous layer is separated
  5. extractionextracted with EtOAc (2×10 mL)
  6. dry with materialThe extracts are dried (MgSO4)
  7. filtrationfiltered through a short pad of SiO2

出典と根拠

ORDレコード
ord-5d36eeb1752c415785976090838f4db3
出典データセット
uspto-grants-2009_04
特許番号
US07517889B2

反応ノート

読み込み中…