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

HRID 2264568Notes

Reaction equation

HRID 2264568 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.[NH2:41][C:42]1[N:47]=[CH:46][N:45]=[C:44]([O:48][C:49]2[CH:50]=[C:51]3[C:56](=[CH:57][CH:58]=2)[NH:55][CH2:54][CH2:53][CH2:52]3)[CH:43]=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:55]3[C:56]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:58][CH:57]=4)[CH2:52][CH2:53][CH2:54]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 595964216-Amino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine

Product 1

HCID 116926456-(6-Amino-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 83 mg (0.28 mMol) of triphosgene in 10 ml of CH2Cl2 is cooled to 2° C. Then a solution of 260 mg (0.86 mMol) of 3-(4-isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-aniline and 171 μl (1-23 mMol) Et3N in 4 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 200 mg (0.82 mMol) of 6-amino-4-(1,2,3,4-tetrahydro-quinolin-6-yloxy)-pyrimidine (Step 1.3) and 114 μl (0.82 mMol) Et3N in 4 ml of CH2Cl2 is added during 5 min and stirring continued for 2 h at rt. EtOAc and a diluted 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 (SiO2; EtOAc/EtOH/Et3N 90:10:0→90:10:1) gives the title compound: TLC(EtOAc/EtOH/Et3N 90:10:1): Rf=0.15; MS: [M+1]+=570; Anal.: C,H,N,F.

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-345ee244bbcc49f1a4835a50362b7b5a
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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