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 2264572Notes

Reaction equation

HRID 2264572 reaction equation
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]

Participants

8

Reactant 5

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

Product 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

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2 °C

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-385b67a67bf945d7a079d91eeb5b4abf
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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