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

HRID 2264596
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HRID 2264596 반응식
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[F:13][C:14]([F:33])([F:32])[C:15]1[CH:16]=[C:17]([CH2:22][N:23]2[CH2:28][CH2:27][N:26]([CH:29]([CH3:31])[CH3:30])[CH2:25][CH2:24]2)[CH:18]=[C:19]([CH:21]=1)[NH2:20].CCN(CC)CC.[NH2:41][C:42]1[N:47]=[CH:46][N:45]=[C:44]([O:48][C:49]2[CH:50]=[C:51]3[C:55](=[CH:56][CH:57]=2)[NH:54][CH2:53][CH2:52]3)[CH:43]=1>C(Cl)Cl.C([O-])([O-])=O.[Na+].[Na+].O.CCOC(C)=O>[CH:29]([N:26]1[CH2:25][CH2:24][N:23]([CH2:22][C:17]2[CH:18]=[C:19]([NH:20][C:2]([N:54]3[C:55]4[C:51](=[CH:50][C:49]([O:48][C:44]5[CH:43]=[C:42]([NH2:41])[N:47]=[CH:46][N:45]=5)=[CH:57][CH:56]=4)[CH2:52][CH2:53]3)=[O:4])[CH:21]=[C:15]([C:14]([F:13])([F:32])[F:33])[CH:16]=2)[CH2:28][CH2:27]1)([CH3:31])[CH3:30]
참가 물질실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 8471Triethylamine2회HCID 94429TriphosgeneHCID 574314423-(4-Isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-anilineHCID 675304825-(6-amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole

생성물 1

HCID 595964085-(6-Amino-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid [3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-phenyl]-amide

시약·촉매·용매 4

HCID 962Water용매HCID 6344Dichloromethane용매3회HCID 8857Ethyl Acetate용매HCID 10340Sodium Carbonate용매

실험 절차

49 mg (0.16 mMol) triphosgene are dissolved in 5 ml ice-cooled CH2Cl2. Then a solution of 149 mg (0.49 mMol) 5-trifluoromethyl-3-(4-isopropylpiperazin-1-ylmethyl)-aniline and 98 μl (0.70 mMol) Et3N in 2 ml CH2Cl2 is added during 5 min. After 3 additional minutes, the mixture is warmed up to rt by a water bath and then a solution of 0.47 mMol 5-(6-amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole (Step 20.3) and 65 μl (0.47 mMol) Et3N in 2 ml CH2Cl2 is added during 5 min. After 2 h at rt, the mixture is diluted with sat. Na2CO3 solution/water 1:1 and EtOAc, the aqueous phase separated off and extracted twice with EtOAc. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Reversed phase MPLC (Gilson system) gives the title compound: MS: [M+1]+=556; HPLC: AtRet=9.7.

후처리

  1. customthe aqueous phase separated off
  2. extractionextracted twice with EtOAc
  3. washThe organic layers are washed with water and brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated

출처 및 근거

ORD 기록
ord-45e9f3aa833040bf9cb2ccdcb884fb62
출처 데이터셋
uspto-grants-2010_12
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US07855215B2

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