(4-bromo-2-chlorophenyl)methanamine

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

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

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2500 mg, 11549 μmol) in THF (20 mL) at 0° C. was added borane-methyl sulfide complex, 2.0 m sol in THF (28873 μl, 57747 μmol). Ice bath removed and reaction stirred overnight warming to 23° C. Reaction cooled to 0° C. and quenched with MeOH (15 mL). Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL). Organic dried with brine and MgSO4. Organic then concentrated to an oil under reduced pressure and purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil. MS (ESI pos. ion) m/z: 220/222 (MH+). Calc'd exact mass for C7H7BrClN: 219/221 Ice bath removed reaction Reaction cooled to 0° C. quenched with MeOH (15 mL) Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL) Organic dried with brine and MgSO4 Organic then concentrated to an oil under reduced pressure purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2500 mg, 11549 μmol) in THF (20 mL) at 0° C. was added borane-methyl sulfide complex, 2.0 m sol in THF (28873 μl, 57747 μmol). Ice bath removed and reaction stirred overnight warming to 23° C. Reaction cooled to 0° C. and quenched with MeOH (15 mL). Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL). Organic dried with brine and MgSO4. Organic then concentrated to an oil under reduced pressure and purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil. MS (ESI pos. ion) m/z: 220/222 (MH+). Calc'd exact mass for C7H7BrClN: 219/221 Ice bath removed reaction Reaction cooled to 0° C. quenched with MeOH (15 mL) Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL) Organic dried with brine and MgSO4 Organic then concentrated to an oil under reduced pressure purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2500 mg, 11549 μmol) in THF (20 mL) at 0° C. was added borane-methyl sulfide complex, 2.0 m sol in THF (28873 μl, 57747 μmol). Ice bath removed and reaction stirred overnight warming to 23° C. Reaction cooled to 0° C. and quenched with MeOH (15 mL). Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL). Organic dried with brine and MgSO4. Organic then concentrated to an oil under reduced pressure and purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil. MS (ESI pos. ion) m/z: 220/222 (MH+). Calc'd exact mass for C7H7BrClN: 219/221 Ice bath removed reaction Reaction cooled to 0° C. quenched with MeOH (15 mL) Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL) Organic dried with brine and MgSO4 Organic then concentrated to an oil under reduced pressure purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil

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

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

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2500 mg, 11549 μmol) in THF (20 mL) at 0° C. was added borane-methyl sulfide complex, 2.0 m sol in THF (28873 μl, 57747 μmol). Ice bath removed and reaction stirred overnight warming to 23° C. Reaction cooled to 0° C. and quenched with MeOH (15 mL). Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL). Organic dried with brine and MgSO4. Organic then concentrated to an oil under reduced pressure and purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil. MS (ESI pos. ion) m/z: 220/222 (MH+). Calc'd exact mass for C7H7BrClN: 219/221 Ice bath removed reaction Reaction cooled to 0° C. quenched with MeOH (15 mL) Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL) Organic dried with brine and MgSO4 Organic then concentrated to an oil under reduced pressure purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2500 mg, 11549 μmol) in THF (20 mL) at 0° C. was added borane-methyl sulfide complex, 2.0 m sol in THF (28873 μl, 57747 μmol). Ice bath removed and reaction stirred overnight warming to 23° C. Reaction cooled to 0° C. and quenched with MeOH (15 mL). Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL). Organic dried with brine and MgSO4. Organic then concentrated to an oil under reduced pressure and purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil. MS (ESI pos. ion) m/z: 220/222 (MH+). Calc'd exact mass for C7H7BrClN: 219/221 Ice bath removed reaction Reaction cooled to 0° C. quenched with MeOH (15 mL) Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL) Organic dried with brine and MgSO4 Organic then concentrated to an oil under reduced pressure purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil

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

Procedure: To a solution of 3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxylic acid (0.324 g, 0.855 mmol) in N,N-Dimethylformamide (DMF) (25 ml) was added diisopropylethylamine (0.329 ml, 1.881 mmol) followed by 1-(4-bromo-2-chlorophenyl)methanamine (0.286 g, 0.855 mmol) and 1H-1,2,3-benzotriazol-1-yloxy-tris(dimethylamino)-phosphonium hexafluorophosphate (BOP reagent, 0.416 g, 0.940 mmol). The reaction was stirred at room temperature for 3 hours. Saturated NaHCO3 was added to the reaction, at which time white solids precipitated from solution. The solids were filtered, washed with acetonitrile, and dried to provide N-[(4-bromo-2-chlorophenyl)methyl]-3-{[4-methyl-6-(methylamino)-1,3,5-triazin-2-yl]amino}cyclohexanecarboxamide (160 mg, 0.34 mmol, 40%). MS (ES+): m/e 467, 469 [M+H]+. precipitated from solution The solids were filtered washed with acetonitrile dried

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

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2 g, 9.24 mmol) in Tetrahydrofuran (THF) (10 ml) was added aluminum hydride (37.0 ml, 18.48 mmol) in THF. The reaction mixture was acidified with 1N HCl to pH=4. The mixture was washed with ether (2×50 ml). The aqueous layer was separated and it was adjusted with 1N NaOH to pH=10. The mixture was extracted with ether. The organic layer was separated and dried over Na2SO4. The solvent was evacuated to give 1-(4-bromo-2-chlorophenyl)methanamine (1.8 g, 8.2 mmol, 88%). MS (ES+): m/e 220, 222 [M+H]+. The mixture was washed with ether (2×50 ml) The aqueous layer was separated The mixture was extracted with ether The organic layer was separated dried over Na2SO4 The solvent was evacuated

Conditions: temp:23.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-bromo-2-chlorobenzonitrile (2500 mg, 11549 μmol) in THF (20 mL) at 0° C. was added borane-methyl sulfide complex, 2.0 m sol in THF (28873 μl, 57747 μmol). Ice bath removed and reaction stirred overnight warming to 23° C. Reaction cooled to 0° C. and quenched with MeOH (15 mL). Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL). Organic dried with brine and MgSO4. Organic then concentrated to an oil under reduced pressure and purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil. MS (ESI pos. ion) m/z: 220/222 (MH+). Calc'd exact mass for C7H7BrClN: 219/221 Ice bath removed reaction Reaction cooled to 0° C. quenched with MeOH (15 mL) Reaction then partitioned between CHCl3 (100 mL) and 1M NaOH (100 mL) Organic dried with brine and MgSO4 Organic then concentrated to an oil under reduced pressure purified on silica (80 g) eluting with 0>6% 2M NH3 in MeOH/DCM and product isolated as a colorless oil