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

HRID 507474노트

반응식

HRID 507474 반응식
[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

참가 물질

10

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 142844-(Dimethylamino)pyridine촉매HCID 962Water용매HCID 8471Triethylamine용매

반응 조건

온도
20 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-9d161b618f3f4320b512548957bb483c
출처 데이터셋
uspto-grants-2010_08
특허 번호
US07786131B2

반응 노트

불러오는 중…