Dichloromethane → N-(3-(2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

HRID 527434

反応式

HRID 527434 の反応式
[C:1]([NH:5][C:6]1[CH:7]=[C:8]([N:12]2[C:17]3[N:18]=[C:19]([NH:22][C:23]4[CH:28]=[CH:27][C:26]([N:29]5[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]5)=[CH:25][C:24]=4[O:42][CH3:43])[N:20]=[CH:21][C:16]=3[C:15]([CH3:44])=[CH:14][C:13]2=[O:45])[CH:9]=[CH:10][CH:11]=1)(=[O:4])[CH:2]=[CH2:3].C(Cl)Cl.C(O)(C(F)(F)F)=O.C(O)(C(F)(F)F)=O.CC#N>C(O)(C(F)(F)F)=O.O>[CH3:43][O:42][C:24]1[CH:25]=[C:26]([N:29]2[CH2:30][CH2:31][NH:32][CH2:33][CH2:34]2)[CH:27]=[CH:28][C:23]=1[NH:22][C:19]1[N:20]=[CH:21][C:16]2[C:15]([CH3:44])=[CH:14][C:13](=[O:45])[N:12]([C:8]3[CH:7]=[C:6]([NH:5][C:1](=[O:4])[CH:2]=[CH2:3])[CH:11]=[CH:10][CH:9]=3)[C:17]=2[N:18]=1

参加物

6

反応物 4

HCID 6344DichloromethaneHCID 6422Trifluoroacetic acidHCID 21924481TFA acetonitrileHCID 86732036Tert-butyl 4-(4-((8-(3-acrylamidophenyl)-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazine-1-carboxylate

生成物 1

HCID 78319000N-(3-(2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide

試薬・触媒・溶媒 1

HCID 22392675Trifluoroacetic acid water溶媒

実験手順

Crude tert-butyl 4-(4-((8-(3-acrylamidophenyl)-5-methyl-7-oxo-7,8-dihydropyrido[2,3-d]pyrimidin-2-yl)amino)-3-methoxyphenyl)piperazine-1-carboxylate (18b) from the previous step was treated with DCM (5 mL) and TFA (5.0 mL, 64.9 mmol) and allowed to stir at RT for 30 min. The reaction mixture was concentrated and purified on the on an ISCO Combiflash RF (24 g Redisep Gold column, using a gradient of 5-20% 2 M NH3/MeOH in DCM) affording enriched product. It was repurifed on a Gilson (Gemini Phenomenex; 30×150 mm, 5 u, 10-95% 0.1% TFA/CH3CN in 0.1% TFA/water), concentrated in the genevac overnight and then passed through a Silicycle SPE-R66030B-20× SiliaSep OT, 5 g/25 mL carbonate column using 20% MeOH/DCM to remove any residual salt then dried under vacuum affording N-(3-(2-((2-methoxy-4-(piperazin-1-yl)phenyl)amino)-5-methyl-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)phenyl)acrylamide (18) (20.6 mg, 0.040 mmol) as a bright yellow amorphous solid. m/z (ESI, +ve ion) 512.0 (M+H)+. 1H NMR (400 MHz, DMSO-d6) δ ppm 10.33 (1H, s), 8.80 (1H, s), 8.08 (1H, s), 7.87 (1H, d, J=8.2 Hz), 7.57 (1H, s), 7.50 (1H, t, J=8.0 Hz), 7.27 (1H, d, J=8.8 Hz), 6.97 (1H, d, J=8.6 Hz), 6.50 (1H, d, J=2.3 Hz), 6.38-6.48 (1H, m), 6.20-6.35 (2H, m), 5.99 (1H, br. s.), 5.76 (1H, dd, J=10.1, 1.9 Hz), 3.77 (3H, s), 2.87-2.99 (4H, m), 2.74-2.85 (4H, m), 2.46 (3H, s).

後処理

  1. concentrationThe reaction mixture was concentrated
  2. custompurified on the on an ISCO Combiflash RF (24 g Redisep Gold column
  3. customaffording
  4. concentrationconcentrated in the genevac overnight
  5. customto remove any residual salt
  6. customthen dried under vacuum

出典と根拠

ORDレコード
ord-9516989bc48840128c9228fda3d662bc
出典データセット
uspto-grants-2016_05
特許番号
US09346801B2

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