Trifluoroacetic acid → N-(4-m-Tolylamino-pyrido[3,4-d]pyrimidin-6-yl)-acrylamide

HRID 394752ノート

反応式

HRID 394752 の反応式
[NH2:1][C:2]1[N:19]=[CH:18][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([CH3:17])[CH:12]=3)[C:4]=2[CH:3]=1.NC1C=CC=C(C)C=1.ClC1C2C=C(F)N=CC=2N=CN=1.C[O:41][C:42]1C=CC(CN)=[CH:44][CH:43]=1.FC(F)(F)C(O)=O.C(Cl)(=O)C=C>CN(C1C=CN=CC=1)C.O.CCN(CC)CC>[CH3:17][C:13]1[CH:12]=[C:11]([NH:10][C:9]2[C:4]3[CH:3]=[C:2]([NH:1][C:42](=[O:41])[CH:43]=[CH2:44])[N:19]=[CH:18][C:5]=3[N:6]=[CH:7][N:8]=2)[CH:16]=[CH:15][CH:14]=1

参加物

10

反応物 6

HCID 6422Trifluoroacetic acidHCID 7934m-ToluidineHCID 13140Acryloyl chlorideHCID 754524-MethoxybenzylamineHCID 53283756-Amino-4-[(3-methylphenyl)amino]pyrido[3,4-d]pyrimidineHCID 106790414-Chloro-6-fluoropyrido[3,4-D]pyrimidine

生成物 1

HCID 10662351N-(4-m-Tolylamino-pyrido[3,4-d]pyrimidin-6-yl)-acrylamide収率 24%

試薬・触媒・溶媒 3

HCID 142844-(Dimethylamino)pyridine触媒HCID 962Water溶媒HCID 8471Triethylamine溶媒

反応条件

温度
20 °C

実験手順

To a stirred solution of 6-amino-4-[(3-methylphenyl)amino]pyrido[3,4-d]pyrimidine, made from m-toluidine and 4-chloro-6-fluoropyrido[3,4-d]-pyrimidine, followed by p-methoxybenzylamine and trifluoroacetic acid, as described in the previous example (140 mg, 0.56 mmol), DMAP (14 mg) and Et3N (excess, 0.5 mL) at 0° C. under N2 was added acryloyl chloride (2.7 mol eq., 123 μL) dropwise over 3 hours. The reaction was then stirred at 20° C. for 1 hour, diluted with water and extracted with EtOAc. The combined organic extracts were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure before being chromatographed on silica gel eluting with CH2Cl2/EtOAc (1:1) to MeOH/CH2Cl2/EtOAc (2:48:50), to give N-[4-[(3-methylphenyl)amino]pyrido-[3,4-d]pyrimidin-6-yl]acrylamide (41 mg, 24%) as a cream powder, mp (EtOAc/hexane) 221-223° C. (decomp).

後処理

  1. extractionextracted with EtOAc
  2. washThe combined organic extracts were washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. custombefore being chromatographed on silica gel eluting with CH2Cl2/EtOAc (1:1) to MeOH/CH2Cl2/EtOAc (2:48:50)

出典と根拠

ORDレコード
ord-5533adaadb32479fa8dc892c6b292ce5
出典データセット
uspto-grants-2003_08
特許番号
US06602863B1

反応ノート

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