Dimethylamine → Gsk-1070916
Reaktionsgleichung
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:12]([C:13]3[CH:18]=[CH:17][N:16]=[C:15]4[NH:19][C:20]([C:22]5[CH:23]=[C:24](CO)[CH:25]=[CH:26][CH:27]=5)=[CH:21][C:14]=34)=[CH:11][N:10]([CH2:30][CH3:31])[N:9]=2)=[CH:4][CH:3]=1.[CH3:32][N:33]1[CH2:38]COC[CH2:34]1.[CH3:39][NH:40][CH3:41].C1[CH2:46][O:45]CC1>>[CH3:32][N:33]([CH2:38][C:24]1[CH:23]=[C:22]([C:20]2[NH:19][C:15]3=[N:16][CH:17]=[CH:18][C:13]([C:12]4[C:8]([C:5]5[CH:6]=[CH:7][C:2]([NH:1][C:46](=[O:45])[N:40]([CH3:41])[CH3:39])=[CH:3][CH:4]=5)=[N:9][N:10]([CH2:30][CH3:31])[CH:11]=4)=[C:14]3[CH:21]=2)[CH:27]=[CH:26][CH:25]=1)[CH3:34]Komponenten
5
Versuchsvorschrift
To a vigorously stirred solution of (3-{4-[3-(4-aminophenyl)-1-ethyl-1H-pyrazol-4-yl]-1H-pyrrolo[2,3-b]pyridin-2-yl}phenyl)methanol (16.13 g, 39.4 mMol) in THF (400 mL) was added NMM (4.5 mL, 40.9 mMol) followed by p-nitrophenylchloroformate (7.9 g, 39.2 mMol). (The reaction quickly became a fine suspension.) After stirring for 1 h at RT, a solution of 2.0 M dimethylamine in THF (200 mL, 400 mMol) was added. The reaction was stirred an additional 1 h at RT then concentrated to dryness under vacuum. The residue which remained was triturated with a cold solution of aq. 1 N NaOH (100 mL) in ice water (200 mL), filtered, washed with cold water (100 mL), and dried under vacuum. Purification by flash chromatography on silica gel (2 to 10% MeOH/CHCl3) gave the title product (16.67 g, 85% pure containing ˜15% starting aniline by LCMS, 75%) as a yellow solid: MS (ES) m/e 481.4 (M+H)+; 1H NMR (400 MHz, DMSO-d6) 12.14 (d, J=1.8 Hz, 1 H), 8.31 (s, 1 H), 8.26 (s, 1 H), 8.07 (d, J=4.8 Hz, 1 H), 7.83 (s, 1 H), 7.77 (d, J=7.8 Hz, 1 H), 7.42 (d, J=8.6 Hz, 2 H), 7.41 (m, 1 H), 7.29 (m, 1 H), 7.28 (d, J=8.6 Hz, 2 H), 6.79 (s, 1 H), 6.78 (d, J=4.8 Hz, 1 H), 5.26 (t, J=5.7 Hz, 1 H), 4.56 (d, J=5.6 Hz, 2 H), 4.27 (q, J=7.3 Hz, 2 H), 2.91 (s, 6 H), 1.51 (t, J=7.3 Hz, 3 H).