O-Phenylenediamine → N-(2-Amino-phenyl)-3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide

HRID 416210ノート

反応式

HRID 416210 の反応式
[C:1]([Si:5]([CH3:34])([CH3:33])[O:6][CH2:7][CH2:8][N:9]([CH2:21][C:22]1[CH:27]=[CH:26][C:25]([CH:28]=[CH:29][C:30]([OH:32])=O)=[CH:24][CH:23]=1)[CH2:10][CH2:11][C:12]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[NH:14][CH:13]=1)([CH3:4])([CH3:3])[CH3:2].CCN(CC)CC.CN([P+](O[N:53]1N=[N:60][C:55]2[CH:56]=[CH:57][CH:58]=[CH:59][C:54]1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F.C1(N)C=CC=CC=1N.[NH4+].[Cl-]>CN(C=O)C>[NH2:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[NH:60][C:30](=[O:32])[CH:29]=[CH:28][C:25]1[CH:26]=[CH:27][C:22]([CH2:21][N:9]([CH2:8][CH2:7][O:6][Si:5]([C:1]([CH3:2])([CH3:4])[CH3:3])([CH3:34])[CH3:33])[CH2:10][CH2:11][C:12]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:14][CH:13]=2)=[CH:23][CH:24]=1

参加物

7

反応物 5

HCID 7243O-PhenylenediamineHCID 8471Triethylamine2 回HCID 25517Ammonium ChlorideHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 666223893-[4-({[2-(tert-Butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)ethyl]-amino}-methyl)-phenyl]-acrylic acid

生成物 1

HCID 66621918N-(2-Amino-phenyl)-3-[4-({[2-(tert-butyl-dimethyl-silanyloxy)-ethyl]-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide収率 96.3%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

実験手順

To a stirred solution of 4 (1.30 g, 2.72 mmol) in anhydrous DMF (20 mL) at room temperature under nitrogen were added Et3N (330 μl, 3.26 mmol) and BOP reagent (1.32 g, 2.99 mmol), respectively. After 30 min, a solution of 1,2-phenylenediamine (352 mg, 3.26 mmol), Et3N (1.14 mL, 8.15 mmol) in anhydrous DMF (3 mL) was added dropwise. After 3 h the reaction mixture was poured into saturated aqueous solution of NH4Cl, and extracted with AcOEt. The extract was washed with saturated NH4Cl, water and brine, dried over MgSO4, filtered, concentrated and purified by flash chromatography on silica gel (MeOH/CH2Cl2, 5/95 plus several drops of NH4OH), to afford the title compound 5 (1.49 g, 2.62 mmol, 96% yield) as a yellow sticky foam. 1H NMR (300 MHz, DMSO-d6) δ(ppm): 10.78 (s, 1H), 9.40 (s, 1H), 7.59 (d, J=8.0 Hz, 2H), 7.58 (d, J=15.8 Hz, 1H), 7.45 (d, J=7.9 Hz, 2H), 7.40 (t, J=7.7 Hz, 2H), 7.35 (d, J=8.4 Hz, 1H), 7.14 (s, 1H), 7.07 (t, J=7.5 Hz, 1H), 7.05-6.85 (m, 3H), 6.79 (d, J=7.9 Hz, 1H), 6.62 (t, J=7.5 Hz, 1H), 4.98 (bs, 2H), 3.80 (s, 2H), 3.71 (t, J=6.2 Hz, 2H), 2.95-2.75 (m, 4H), 2.71 (t, J=6.2 Hz, 2H), 0.89 (s, 9H), 0.05 (s, 6H).

後処理

  1. extractionextracted with AcOEt
  2. washThe extract was washed with saturated NH4Cl, water and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. custompurified by flash chromatography on silica gel (MeOH/CH2Cl2, 5/95 plus several drops of NH4OH)

出典と根拠

ORDレコード
ord-e832f148225c40c5820f587773b6775d
出典データセット
uspto-grants-2012_01
特許番号
US08088805B2

反応ノート

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