Triethylamine → 6-(6-Methylamino-pyrimidin-4-yloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid [3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-phenyl]-amide

HRID 2264572ノート

反応式

HRID 2264572 の反応式
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[CH:13]([N:16]1[CH2:21][CH2:20][N:19]([CH2:22][C:23]2[CH:24]=[C:25]([CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=2)[NH2:26])[CH2:18][CH2:17]1)([CH3:15])[CH3:14].CCN(CC)CC.[CH3:41][NH:42][C:43]1[N:48]=[CH:47][N:46]=[C:45]([O:49][C:50]2[CH:51]=[C:52]3[C:57](=[CH:58][CH:59]=2)[NH:56][CH2:55][CH2:54][CH2:53]3)[CH:44]=1.C([O-])([O-])=O.[Na+].[Na+]>C(Cl)Cl.CCOC(C)=O>[CH:13]([N:16]1[CH2:17][CH2:18][N:19]([CH2:22][C:23]2[CH:24]=[C:25]([NH:26][C:2]([N:56]3[C:57]4[C:52](=[CH:51][C:50]([O:49][C:45]5[CH:44]=[C:43]([NH:42][CH3:41])[N:48]=[CH:47][N:46]=5)=[CH:59][CH:58]=4)[CH2:53][CH2:54][CH2:55]3)=[O:4])[CH:27]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:29]=2)[CH2:20][CH2:21]1)([CH3:15])[CH3:14]

参加物

8

反応物 5

HCID 8471Triethylamine2 回HCID 10340Sodium CarbonateHCID 94429TriphosgeneHCID 574314423-(4-Isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-anilineHCID 675311756-Methylamino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine

生成物 1

HCID 115198946-(6-Methylamino-pyrimidin-4-yloxy)-3,4-dihydro-2H-quinoline-1-carboxylic acid [3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-phenyl]-amide

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
2 °C

実験手順

A solution of 41 mg (0.138 mMol) of triphosgene in 5 ml of CH2Cl2 is cooled to 2° C. Then a solution of 123 mg (0.41 mMol) of 3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-aniline and 82 μl (0.59 mMol) Et3N in 2 ml CH2Cl2 is added during 5 min. The mixture is stirred for 3 min at 2° C. and then warmed up to rt in a water bath. A solution of 100 mg (0.39 mMol) of 6-methylamino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine (Step 3.2) and 54 μl (0.39 mMol) Et3N in 2 ml of CH2Cl2 is added during 5 min and stirring continued for 2 h at rt. EtOAc and a sat. solution of Na2CO3 is added to the reaction mixture. The aqueous phase is separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (Combi Flash; EtOAc/EtOH/Et3N 95:5:0→90:10→90:10:1) gives the title compound: MS: [M+1]+=584; TLC(EtOAc/EtOH/NH3conc. 90:10:1): Rf=0.11; HPLC: AtRet=10.1.

後処理

  1. temperaturewarmed up to rt in a water bath
  2. stirringstirring
  3. waitcontinued for 2 h at rt
  4. customThe aqueous phase is separated off
  5. extractionextracted twice with EtOAc
  6. washThe organic layers are washed with water and brine
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated

出典と根拠

ORDレコード
ord-385b67a67bf945d7a079d91eeb5b4abf
出典データセット
uspto-grants-2010_12
特許番号
US07855215B2

反応ノート

読み込み中…