Hydrochloric Acid → N-(2,6-difluorophenyl)-5-(7-fluoro-3-{2-[(2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide

HRID 419623ノート

反応式

HRID 419623 の反応式
Cl[C:2]1[N:7]=[C:6]([C:8]2[N:12]3[CH:13]=[CH:14][C:15]([F:17])=[CH:16][C:11]3=[N:10][C:9]=2[C:18]2[CH:19]=[CH:20][C:21]([O:35][CH3:36])=[C:22]([CH:34]=2)[C:23]([NH:25][C:26]2[C:31]([F:32])=[CH:30][CH:29]=[CH:28][C:27]=2[F:33])=[O:24])[CH:5]=[CH:4][N:3]=1.[CH3:37][O:38][C:39]1[CH:45]=[C:44]([N:46]2[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]2)[CH:43]=[CH:42][C:40]=1[NH2:41].Cl.O1CCOCC1.C[O-].[Na+]>FC(F)(F)CO.CO.C(Cl)Cl.CCCCCC>[F:33][C:27]1[CH:28]=[CH:29][CH:30]=[C:31]([F:32])[C:26]=1[NH:25][C:23](=[O:24])[C:22]1[CH:34]=[C:18]([C:9]2[N:10]=[C:11]3[CH:16]=[C:15]([F:17])[CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:41][C:40]3[CH:42]=[CH:43][C:44]([N:46]4[CH2:51][CH2:50][CH:49]([CH2:52][CH2:53][S:54]([CH3:57])(=[O:56])=[O:55])[CH2:48][CH2:47]4)=[CH:45][C:39]=3[O:38][CH3:37])[N:7]=2)[CH:19]=[CH:20][C:21]=1[O:35][CH3:36]

参加物

10

反応物 5

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 10942334Sodium MethoxideHCID 594529085-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluorophenyl)-2-(methyloxy)benzamideHCID 666497682-(Methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline

生成物 1

HCID 59452797N-(2,6-difluorophenyl)-5-(7-fluoro-3-{2-[(2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(methyloxy)benzamide収率 77.3%

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 64092,2,2-Trifluoroethanol溶媒HCID 8058Hexane溶媒

反応条件

温度
170 °C

実験手順

To 5-[3-(2-chloro-4-pyrimidinyl)-7-fluoroimidazo[1,2-a]pyridin-2-yl]-N-(2,6-difluoro-phenyl)-2-(methyloxy)benzamide (Example 197, step A) (126 mg, 0.25 mmol) and 2-(methyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (Example 200, step B) (70 mg, 0.22 mmol) in 2,2,2-trifluoroethanol (1.0 mL) was added 4 M HCl in dioxane (112 μL, 0.45 mmol). The mixture was stirred and heated on a microwave at 170° C. for 45 min, then cooled to rt. The mixture was neutralized with 0.5M sodium methoxide in MeOH. The mixture was concentrated under vacuum and the residue purified by silica gel chromatography to give a yellow oil. The oil was dissolved in minimal DCM, then hexane was added until a precipitate was formed. The slurry was cooled at −10° C. for 30 min, then poured through a Teflon filter, washing the solids with cold hexanes. The solids were dried under vacuum to give the title compound (135 mg, 0.17 mmol, 77%) as a yellow solid. 1H NMR (400 MHz, DMSO-d6): 6 ppm 9.80 (s, 1H), 9.40-9.53 (m, 1H), 8.50 (s, 1H), 8.21 (d, J=5.1 Hz, 1H), 8.11 (d, J=1.3 Hz, 1H), 7.79 (d, J=8.4 Hz, 1H), 7.59 (dd, J=9.5, 2.4 Hz, 1H), 7.33-7.46 (m, 2H), 7.30 (d, J=8.6 Hz, 1H), 7.20 (t, J=8.1 Hz, 2H), 6.97-7.07 (m, 1H), 6.70 (d, J=1.6 Hz, 1H), 6.45-6.58 (m, 2H), 4.00 (s, 3H), 3.81 (s, 3H), 3.70-3.75 (m, 2H), 3.14-3.22 (m, 2H), 2.97 (s, 3H), 2.64 (t, J=11.4 Hz, 2H), 1.74-1.85 (m, 2H), 1.62-1.72 (m, 2H), 1.46-1.58 (m, 1H), 1.21-1.37 (m, 2H). MS (ESI): 785 [M+H]+.

後処理

  1. temperaturecooled to rt
  2. concentrationThe mixture was concentrated under vacuum
  3. customthe residue purified by silica gel chromatography
  4. customto give a yellow oil
  5. customwas formed
  6. temperatureThe slurry was cooled at −10° C. for 30 min
  7. filtrationfilter
  8. washwashing the solids with cold hexanes
  9. customThe solids were dried under vacuum

出典と根拠

ORDレコード
ord-e25e0aaf5e664f1397b6e8e25664f11b
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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