Ammonia → 5-(3-(2-[(5-chloro-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide

HRID 419612ノート

反応式

HRID 419612 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]3=[N:10][C:9]=2[C:17]2[CH:18]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=2)[C:22]([NH:24][C:25]2[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=2[F:32])=[O:23])[CH:5]=[CH:4][N:3]=1.[Cl:37][C:38]1[C:39]([N:47]2[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH2:49][CH2:48]2)=[CH:40][C:41]([O:45][CH3:46])=[C:42]([CH:44]=1)[NH2:43].C1(C)C=CC(S([O-])(=O)=O)=CC=1.[NH+]1C=CC=CC=1.N>CC(O)C.CO>[Cl:37][C:38]1[C:39]([N:47]2[CH2:52][CH2:51][N:50]([CH2:53][CH2:54][S:55]([CH3:58])(=[O:57])=[O:56])[CH2:49][CH2:48]2)=[CH:40][C:41]([O:45][CH3:46])=[C:42]([NH:43][C:2]2[N:7]=[C:6]([C:8]3[N:12]4[CH:13]=[CH:14][CH:15]=[CH:16][C:11]4=[N:10][C:9]=3[C:17]3[CH:18]=[CH:19][C:20]([O:34][CH2:35][CH3:36])=[C:21]([CH:33]=3)[C:22]([NH:24][C:25]3[C:30]([F:31])=[CH:29][CH:28]=[CH:27][C:26]=3[F:32])=[O:23])[CH:5]=[CH:4][N:3]=2)[CH:44]=1

参加物

7

反応物 4

HCID 222AmmoniaHCID 466102Benzenesulfonic acid, 4-methyl-, compd. with pyridine (1:1)HCID 594528825-Chloro-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}anilineHCID 594529415-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide

生成物 1

HCID 594527535-(3-(2-[(5-chloro-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide収率 38%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 3776Isopropanol溶媒

反応条件

温度
80 °C

実験手順

In a 10 mL vial with septum cap, 5-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(ethyloxy)benzamide (Intermediate Example 6) (0.200 g, 0.395 mmol), 5-chloro-2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperazinyl}aniline (0.165 g, 0.474 mmol) were taken up in iPrOH (3 mL) and pyridinium p-toluenesulfonate (0.238 g, 0.949 mmol) was added. The vial was sealed and heated to 80° C. overnight. When reaction was complete by MS, it was cooled to rt, neutralized with 7N ammonia in MeOH, absorbed onto silica gel and flash chromatographed. Fractions containing the desired product were concentrated and the resulting solid was triturated with diethyl ether, filtered and air dried to give the title compound (0.12 g, 0.15 mmol, 37%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.71 (s, 1H), 9.38 (dd, J=4.4, 1.1 Hz, 1H), 8.53 (s, 1H), 8.25 (d, J=5.3 Hz, 1H), 8.02 (d, J=0.4 Hz, 1H), 7.87 (s, 1H), 7.63-7.79 (m, 2H), 7.28-7.50 (m, 2H), 7.10-7.28 (m, 3H), 6.97 (t, J=6.9 Hz, 1H), 6.82 (s, 1H), 6.60 (d, J=5.2 Hz, 1H), 4.23 (q, J=6.7 Hz, 2H), 3.83 (s, 3H), 3.27-3.34 (m, 2H), 3.03 (s, 3H), 2.93-3.01 (m, 4H), 2.75 (t, J=6.6 Hz, 2H), 2.51-2.64 (m, 4H), 1.40 (t, J=6.8 Hz, 3H). MS (M+H, ES+) 817.

後処理

  1. customIn a 10 mL vial with septum cap
  2. customThe vial was sealed
  3. customWhen reaction
  4. temperaturewas cooled to rt
  5. customabsorbed onto silica gel and flash
  6. customchromatographed
  7. additionFractions containing the desired product
  8. concentrationwere concentrated
  9. customthe resulting solid was triturated with diethyl ether
  10. filtrationfiltered
  11. customair dried

出典と根拠

ORDレコード
ord-25435685944d41e9892ff5674f203ddd
出典データセット
uspto-grants-2012_01
特許番号
US08093239B2

反応ノート

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