4-(4-Ethyl-piperazin-1-ylmethyl)-phenylamine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A suspension of 1-ethyl-4-(4-nitro-benzyl)-piperazine (7.2 g, 29.14 mmol) and Raney Nickel (1.5 g) in MeOH (100 mL) is stirred for 6 h at RT, under a hydrogen atmosphere. The reaction mixture is filtered through a pad of celite and concentrated to afford 6.3 g of the title compound as a yellow solid: ESI-MS: 220.1 [MH]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1). The reaction mixture is filtered through a pad of celite concentrated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 104 mg (0.35 mMol) triphosgene are dissolved in 13 ml ice-cooled CH2Cl2. Then a solution of 230 mg (1.05 mMol) 4-(4-ethylpiperazin-1-ylmethyl)-aniline and 209 μl (1.50 mMol) Et3N in 6 ml CH2Cl2 is added during 8 min. After 3 additional minutes, the mixture is warmed up to rt by a water bath and then a solution of 1.0 mMol 5-(6-chloro-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole (Step 14.1) and 139 μl (1.00 mMol) Et3N in 6 ml CH2Cl2 is added during 8 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. Crystallization from DIPE gives the title compound: MS: [M+1]+=493/495; TLC(CH2Cl2/MeOH/NH3conc. 90:10:1): Rf=0.24; HPLC: AtRet=10.5. the aqueous phase separated off extracted twice with EtOAc The organic layers are washed with water and brine dried (Na2SO4) concentrated Crystallization from DIPE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 104 mg (0.35 mMol) triphosgene are dissolved in 13 ml ice-cooled CH2Cl2. Then a solution of 230 mg (1.05 mMol) 4-(4-ethylpiperazin-1-ylmethyl)-aniline and 209 μl (1.50 mMol) Et3N in 6 ml CH2Cl2 is added during 8 min. After 3 additional minutes, the mixture is warmed up to rt by a water bath and then a solution of 1.0 mMol 5-(6-chloro-pyrimidin-4-yloxy)-2,3-dihydro-1H-indole (Step 14.1) and 139 μl (1.00 mMol) Et3N in 6 ml CH2Cl2 is added during 8 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. Crystallization from DIPE gives the title compound: MS: [M+1]+=493/495; TLC(CH2Cl2/MeOH/NH3conc. 90:10:1): Rf=0.24; HPLC: AtRet=10.5. the aqueous phase separated off extracted twice with EtOAc The organic layers are washed with water and brine dried (Na2SO4) concentrated Crystallization from DIPE

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was prepared in analogy to the procedure described in Step 11.1 but using 1-ethyl-4-(4-nitro-benzyl)-piperazine (Step 12.2): ESI-MS: 220.1 [M+H]+; TLC: Rf=0.08 (DCM/MeOH+1% NH3aq, 9:1).