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

HRID 2264596Notes

Reaction equation

HRID 2264596 reaction equation
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]

Participants

9

Reactant 4

HCID 8471Triethylamine2×HCID 94429TriphosgeneHCID 574314423-(4-Isopropylpiperazin-1-ylmethyl)-5-trifluoromethyl-anilineHCID 675304825-(6-amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole

Product 1

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

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×HCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-45e9f3aa833040bf9cb2ccdcb884fb62
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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