4-Chloro-3-(trifluoromethyl)aniline → 5-(2-Amino-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (4-chloro-3-trifluoromethyl-phenyl)-amide

HRID 2264616Notes

Reaction equation

HRID 2264616 reaction equation
Cl[C:2](Cl)([O:4]C(=O)OC(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:15]=[CH:16][C:17]([Cl:24])=[C:18]([C:20]([F:23])([F:22])[F:21])[CH:19]=1.C(N(C(C)C)C(C)C)C.[NH2:34][C:35]1[N:40]=[C:39]([O:41][C:42]2[CH:43]=[C:44]3[C:48](=[CH:49][CH:50]=2)[NH:47][CH2:46][CH2:45]3)[CH:38]=[CH:37][N:36]=1>C(Cl)Cl.C1COCC1.C([O-])(O)=O.[Na+]>[Cl:24][C:17]1[CH:16]=[CH:15][C:14]([NH:13][C:2]([N:47]2[C:48]3[C:44](=[CH:43][C:42]([O:41][C:39]4[CH:38]=[CH:37][N:36]=[C:35]([NH2:34])[N:40]=4)=[CH:50][CH:49]=3)[CH2:45][CH2:46]2)=[O:4])=[CH:19][C:18]=1[C:20]([F:21])([F:22])[F:23]

Participants

8

Reactant 4

HCID 675744-Chloro-3-(trifluoromethyl)anilineHCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 675302915-(2-Amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole

Product 1

HCID 595964035-(2-Amino-pyrimidin-4-yloxy)-2,3-dihydro-indole-1-carboxylic acid (4-chloro-3-trifluoromethyl-phenyl)-amide

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Procedure

90 mg (0.30 mMol) triphosgene are dissolved in 5 ml ice-cooled CH2Cl2. Then a solution of 148 mg (0.76 mMol) 5-amino-2-chloro-benzotrifluoride and 0.3 ml (1.72 mMol) EtN(iPr)2 in 5 ml CH2Cl2 is added during 15 min. After stirring the reaction mixture for further 15 min, a solution of 200 mg (0.88 mMol) 5-(2-amino-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole (Step 26.2) and 0.3 ml (1.72 mMol) EtN(iPr)2 in 5 ml THF is added. After 16 h at rt, the mixture is diluted with 10% NaHCO3 solution and CH2Cl2, the aqueous phase separated off and extracted twice with CH2Cl2. The organic layers are washed with water and brine, dried (Na2SO4) and concentrated. Column chromatography (SiO2; 1% MeOH in CHCl3) gives the title compound: MS: [M+1]+=450; HPLC: EtRet=3.7.

Workup

  1. waitAfter 16 h at rt
  2. customthe aqueous phase separated off
  3. extractionextracted twice with CH2Cl2
  4. washThe organic layers are washed with water and brine
  5. dry with materialdried (Na2SO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-bc1701a2034844859c54f9916ecd63f0
Source dataset
uspto-grants-2010_12
Patent number
US07855215B2

Reaction notes

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