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

HRID 419606
ノート
印刷プレビュー

反応式

HRID 419606 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.[CH2:37]([C:39]1[C:40]([N:49]2[CH2:54][CH2:53][CH:52]([CH2:55][CH2:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH2:51][CH2:50]2)=[CH:41][C:42]([O:46][CH2:47][CH3:48])=[C:43]([CH:45]=1)[NH2:44])[CH3:38].Cl.O1CCOCC1.N>CO>[F:32][C:26]1[CH:27]=[CH:28][CH:29]=[C:30]([F:31])[C:25]=1[NH:24][C:22](=[O:23])[C:21]1[CH:33]=[C:17]([C:9]2[N:10]=[C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][N:12]3[C:8]=2[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([NH:44][C:43]3[CH:45]=[C:39]([CH2:37][CH3:38])[C:40]([N:49]4[CH2:50][CH2:51][CH:52]([CH2:55][CH2:56][S:57]([CH3:60])(=[O:59])=[O:58])[CH2:53][CH2:54]4)=[CH:41][C:42]=3[O:46][CH2:47][CH3:48])[N:7]=2)[CH:18]=[CH:19][C:20]=1[O:34][CH2:35][CH3:36]
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

7

反応物 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 594526665-Ethyl-2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}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 59452613
N-(2,6-difluorophenyl)-5-(3-{2-[(5-ethyl-2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}phenyl)amino]-4-pyrimidinyl}imidazo[1,2-a]pyridin-2-yl)-2-(ethyloxy)benzamide
収率 58%

試薬・触媒・溶媒 1

HCID 887Methanol溶媒

反応条件

温度
180 °C

実験手順

In a microwave 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) (0.148 g, 0.293 mmol) and 5-ethyl-2-(ethyloxy)-4-{4-[2-(methylsulfonyl)ethyl]-1-piperidinyl}aniline (0.104 g, 0.293 mmol) were taken up in 1,1,1-trifluoroethanol (1.5 mL) and 4M HCl in dioxane (0.147 mL, 0.587 mmol) 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 to rt, neutralized with 7N ammonia in MeOH, and concentrated in vacuo onto silica gel and flash chromatographed. The desired fractions were combined and concentrated and the resulting solid was triturated with diethyl ether, filtered and air dried to give the title compound (0.14 g, 0.17 mmol, 58%). 1H NMR (400 MHz, DMSO-d6) δ ppm 9.70 (s, 1H), 9.29 (d, J=6.8 Hz, 1H), 8.34 (s, 1H), 8.23 (d, J=5.2 Hz, 1H), 8.03 (s, 1H), 7.61-7.79 (m, 2H), 7.55 (s, 1H), 7.29-7.48 (m, 2H), 7.08-7.28 (m, 3H), 6.89 (t, J=6.8 Hz, 1H), 6.76 (s, 1H), 6.56 (d, J=5.1 Hz, 1H), 4.23 (q, J=6.7 Hz, 2H), 4.03 (q, J=6.9 Hz, 2H), 3.07-3.20 (m, 2H), 2.84-3.04 (m, 5H), 2.60 (t, J=10.9 Hz, 2H), 2.51 (q, J=7.5 Hz, 2H), 1.75 (d, J=11.2 Hz, 2H), 1.60-1.70 (m, 2H), 1.35-1.55 (m, 4H), 1.15-1.36 (m, 5H), 1.05 (td, J=7.2, 1.9 Hz, 3H). MS (M+H, ES+) 824.

後処理

  1. customIn a microwave vial with septum cap
  2. customThe vial was sealed
  3. customReaction
  4. temperaturewas cooled to rt
  5. concentrationconcentrated in vacuo onto silica gel and flash
  6. customchromatographed
  7. concentrationconcentrated
  8. customthe resulting solid was triturated with diethyl ether
  9. filtrationfiltered
  10. customair dried

出典と根拠

ORDレコード
ord-9659ff71c22b4b69bf2f135710f5cec1
出典データセット
uspto-grants-2012_01
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08093239B2

反応ノート

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このページの内容参加物反応条件実験手順後処理出典と根拠反応ノート