Ammonia → 3-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2,5-bis(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide

HRID 419419ノート

反応式

HRID 419419 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]=[C:19]([CH:31]=[CH:32][CH:33]=2)[C:20]([NH:22][C:23]2[C:28]([F:29])=[CH:27][CH:26]=[CH:25][C:24]=2[F:30])=[O:21])[CH:5]=[CH:4][N:3]=1.[N:34]1([CH:40]2[CH2:45][CH2:44][N:43]([C:46]3[C:52]([O:53][CH3:54])=[CH:51][C:49]([NH2:50])=[C:48]([O:55][CH3:56])[CH:47]=3)[CH2:42][CH2:41]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1.N>CC(O)C.Cl.CO>[N:34]1([CH:40]2[CH2:41][CH2:42][N:43]([C:46]3[C:52]([O:53][CH3:54])=[CH:51][C:49]([NH:50][C:2]4[N:7]=[C:6]([C:8]5[N:12]6[CH:13]=[CH:14][CH:15]=[CH:16][C:11]6=[N:10][C:9]=5[C:17]5[CH:18]=[C:19]([CH:31]=[CH:32][CH:33]=5)[C:20]([NH:22][C:23]5[C:24]([F:30])=[CH:25][CH:26]=[CH:27][C:28]=5[F:29])=[O:21])[CH:5]=[CH:4][N:3]=4)=[C:48]([O:55][CH3:56])[CH:47]=3)[CH2:44][CH2:45]2)[CH2:39][CH2:38][CH2:37][CH2:36][CH2:35]1

参加物

7

反応物 3

HCID 222AmmoniaHCID 594526104-(1,4'-Bipiperidin-1'-yl)-2,5-bis(methyloxy)anilineHCID 594529693-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide

生成物 1

HCID 594526443-[3-(2-{[4-(1,4'-bipiperidin-1'-yl)-2,5-bis(methyloxy)phenyl]amino}-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)benzamide収率 40.3%

試薬・触媒・溶媒 3

HCID 313Hydrochloric Acid触媒HCID 887Methanol溶媒HCID 3776Isopropanol溶媒

反応条件

温度
180 °C

実験手順

In a 5 mL microwave vial with septum cap, 3-[3-(2-chloro-4-pyrimidinyl)imidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1) (0.200 g, 0.433 mmol), 4-(1,4′-bipiperidin-1′-yl)-2,5-bis(methyloxy)aniline (0.166 g, 0.520 mmol) were taken up in iPrOH (3 mL) and concentrated HCl (4 drops) was added. The vial was sealed and heated in the microwave at 180° C. for 40 min. Reaction was complete by MS, it was cooled rt, neutralized with 7N ammonia in MeOH, and concentrated in vacuo. The resulting residue was taken up in DCM and purified by column chromatography using basic alumina. The desired combined fractions were concentrated and the resulting solid was triturated with DCM and hexane, filtered and air dried to give the title compound (0.130 g, 40%). 1H NMR (400 MHz, DMSO-d6) δ ppm 10.23 (s, 1H), 9.41 (br. s., 1H), 8.50 (s, 1H), 8.33 (s, 1H), 8.24 (d, J=5.1 Hz, 1H), 8.05 (d, J=7.7 Hz, 1H), 7.83 (d, J=8.1 Hz, 1H), 7.73 (d, J=9.2 Hz, 1H), 7.60 (t, J=7.9 Hz, 1H), 7.43-7.50 (m, 1H), 7.36-7.42 (m, 1H), 7.34 (s, 1H), 7.20 (t, J=8.1 Hz, 2H), 6.94-7.00 (m, 1H), 6.66 (s, 1H), 6.50 (d, J=5.1 Hz, 1H), 3.76 (s, 3H), 3.64 (s, 3H), 3.43 (d, J=11.7 Hz, 2H), 2.51-2.58 (m, 2H), 2.26-2.35 (m, 1H), 1.77 (d, J=13.6 Hz, 2H), 1.53-1.64 (m, 2H), 1.48 (s, 4H), 1.38 (s, 2H). MS (M+H, ES+) 745.

後処理

  1. customIn a 5 mL microwave vial with septum cap
  2. customThe vial was sealed
  3. customReaction
  4. temperaturewas cooled rt
  5. concentrationconcentrated in vacuo
  6. custompurified by column chromatography
  7. concentrationwere concentrated
  8. customthe resulting solid was triturated with DCM and hexane
  9. filtrationfiltered
  10. customair dried

出典と根拠

ORDレコード
ord-17191fd4eeb9499388f44cb71ecaf448
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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