(4-chlorophenyl)urea

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

Procedure: 4-Chlorophenyl urea (8.5 parts) and a solution of sodium nitrite (6.9 parts) in water (10 parts) were added over 6 hours to a mixture of conc. hydrochloric acid (10.3 parts) chloroform (130 parts) and tetra-n-butyl ammonium fluoroborate (10% by weight based on 4-chlorophenyl urea) at -10° to -5° C. The mixture was stirred for a further 15 minutes then the stirrer stopped and layers allowed to separate. No solid was present at this stage. 5 mls of the organic layer was taken for analysis and the remainder kept cold until required. to separate

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

Procedure: 4-Chlorophenyl urea (8.5 parts) and a solution of sodium nitrite (6.9 parts) in water (10 parts) were added over 6 hours to a mixture of conc. hydrochloric acid (10.3 parts) chloroform (130 parts) and tetra-n-butyl ammonium fluoroborate (10% by weight based on 4-chlorophenyl urea) at -10° to -5° C. The mixture was stirred for a further 15 minutes then the stirrer stopped and layers allowed to separate. No solid was present at this stage. 5 mls of the organic layer was taken for analysis and the remainder kept cold until required. to separate

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

Procedure: A mixture of 0.15 mole each of p-chlorophenylurea, phenyl diphenylphosphinite, and n-butylraldehyde in 150g of toluene is warmed at reflux for 5.5 hr, giving a reaction mixture having a 31P nmr signal only at -36.8 ppm. When the toluene is removed at reduced pressure, the residue solidifies. Recrystallization of a portion from benzene gives a white solid: mp 275°-278° C.; 31P nmr -37.4 ppm; 1H nmr δ9.1 (s, 1, NHC6H4Cl), 6.4-8.1 (m, 15, aryl and CHNH), 5.1 (m, 1, PCH), 0.6-2.0 (m, 7, CH2CH2CH3). is warmed at reflux for 5.5 hr giving a reaction mixture When the toluene is removed at reduced pressure Recrystallization of a portion from benzene gives a white solid

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

Procedure: A mixture of 0.15 mole each of p-chlorophenylurea, phenyl diphenylphosphinite, and n-butylraldehyde in 150g of toluene is warmed at reflux for 5.5 hr, giving a reaction mixture having a 31P nmr signal only at -36.8 ppm. When the toluene is removed at reduced pressure, the residue solidifies. Recrystallization of a portion from benzene gives a white solid: mp 275°-278° C.; 31P nmr -37.4 ppm; 1H nmr δ9.1 (s, 1, NHC6H4Cl), 6.4-8.1 (m, 15, aryl and CHNH), 5.1 (m, 1, PCH), 0.6-2.0 (m, 7, CH2CH2CH3). is warmed at reflux for 5.5 hr giving a reaction mixture When the toluene is removed at reduced pressure Recrystallization of a portion from benzene gives a white solid

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

Procedure: A mixture of 0.15 mole each of p-chlorophenylurea, phenyl diphenylphosphinite, and n-butyraldehyde in 150g of toluene is warmed at reflux for 5.5 hr, giving a reaction mixture having a 31P nmr signal only at -36.8 ppm. When the toluene is removed at reduced pressure, the residue solidifies. Recrystallization of a portion from benzene gives a white solid: mp 275°-278°C; 31P nmr -37.4 ppm; 1H nmr δ9.1 (s, 1, NHC6H4C1), 6.4-8.1 (m, 15, aryl and CHNH), 5.1 (m, 1, PCH), 0.6-2.0 (m, 7, CH2CH2CH3). is warmed at reflux for 5.5 hr giving a reaction mixture When the toluene is removed at reduced pressure Recrystallization of a portion from benzene gives a white solid

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

Procedure: To a stirred solution of Example C (1.60 g, 3.63 mmol) in THF (200 mL) was added LiAlH4 powder (413 mg, 10.9 mmol) at −10° C. under N2. The mixture was stirred for 2 h and excess LiAlH4 was quenched by adding ice. The solution was acidified to pH=7 with dilute HCl. Solvents were slowly removed and the solid was filtered and washed with EtOAc (200+100 mL). The filtrate was concentrated to yield 1-{3-tert-butyl-1-[3-hydroxymethyl)phenyl]-1H-pyrazol-5-yl}-3-(4-chlorophenyl)urea (1.40 g, 97%). 1H NMR (DMSO-d6): δ 9.11 (s, 1H), 8.47 (s, 1H), 7.47–7.27 (m, 8H), 6.35 (s, 1H), 5.30 (t, J=5.6 Hz, 1H), 4.55 (d, J=5.6 Hz, 2H), 1.26 (s, 9H); MS (ESI) m/z: 399 (M+H+). excess LiAlH4 was quenched by adding ice Solvents were slowly removed the solid was filtered washed with EtOAc (200+100 mL) The filtrate was concentrated

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

Procedure: To a stirred solution of Example C (1.60 g, 3.63 mmol) in THF (200 mL) was added LiAlH4 powder (413 mg, 10.9 mmol) at −10° C. under N2. The mixture was stirred for 2 h and excess LiAlH4 was quenched by adding ice. The solution was acidified to pH=7 with dilute HCl. Solvents were slowly removed and the solid was filtered and washed with EtOAc (200+100 mL). The filtrate was concentrated to yield 1-{3-tert-butyl-1-[3-hydroxymethyl)phenyl]-1H-pyrazol-5-yl}-3-(4-chlorophenyl)urea (1.40 g, 97%). 1H NMR (DMSO-d6): δ 9.11 (s, 1H), 8.47 (s, 1H), 7.47-7.27 (m, 8H), 6.35 (s, 1H), 5.30 (t, J=5.6 Hz, 1H), 4.55 (d, J=5.6 Hz, 2H), 1.26 (s, 9H); MS (ESI) m/z: 399 (M+H+). excess LiAlH4 was quenched by adding ice Solvents were slowly removed the solid was filtered washed with EtOAc (200+100 mL) The filtrate was concentrated

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

Procedure: A mixture of 0.15 mole each of p-chlorophenylurea, phenyl diphenylphosphinite, and n-butyraldehyde in 150g of toluene is warmed at reflux for 5.5 hr, giving a reaction mixture having a 31P nmr signal only at 3136.8 ppm. When the toluene is removed at reduced pressure, the residue solidifies. Recrystallization of a portion from benzene gives a white solid: mp 275°-278° C; 31P nmr -37.4 ppm; 1H nmr δ9.1 (s, 1, NHC6H4Cl), 6.4-8.1 (m, 15, aryl and CHNH), 5.1 (m, 1, PCH), 0.6-2.0 (m, 7, CH2CH2CH3). is warmed at reflux for 5.5 hr giving a reaction mixture When the toluene is removed at reduced pressure Recrystallization of a portion from benzene gives a white solid

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

Procedure: 4-Chlorophenyl urea (8.5 parts) and a solution of sodium nitrite (6.9 parts) in water (10 parts) were added over 6 hours to a mixture of conc. hydrochloric acid (10.3 parts) chloroform (130 parts) and tetra-n-butyl ammonium fluoroborate (10% by weight based on 4-chlorophenyl urea) at -10° to -5° C. The mixture was stirred for a further 15 minutes then the stirrer stopped and layers allowed to separate. No solid was present at this stage. 5 mls of the organic layer was taken for analysis and the remainder kept cold until required. to separate

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

Procedure: A mixture of 0.15 mole each of p-chlorophenylurea, phenyl diphenylphosphinite, and n-butylraldehyde in 150g of toluene is warmed at reflux for 5.5 hr, giving a reaction mixture having a 31P nmr signal only at -36.8 ppm. When the toluene is removed at reduced pressure, the residue solidifies. Recrystallization of a portion from benzene gives a white solid: mp 275°-278° C.; 31P nmr -37.4 ppm; 1H nmr δ9.1 (s, 1, NHC6H4Cl), 6.4-8.1 (m, 15, aryl and CHNH), 5.1 (m, 1, PCH), 0.6-2.0 (m, 7, CH2CH2CH3). is warmed at reflux for 5.5 hr giving a reaction mixture When the toluene is removed at reduced pressure Recrystallization of a portion from benzene gives a white solid

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

Procedure: To a stirred solution of Example C (1.60 g, 3.63 mmol) in THF (200 mL) was added LiAlH4 powder (413 mg, 10.9 mmol) at −10° C. under N2. The mixture was stirred for 2 h and excess LiAlH4 was quenched by adding ice. The solution was acidified to pH=7 with dilute HCl. Solvents were slowly removed and the solid was filtered and washed with EtOAc (200+100 mL). The filtrate was concentrated to yield 1-{3-tert-butyl-1-[3-hydroxymethyl)phenyl]-1H-pyrazol-5-yl}-3-(4-chlorophenyl)urea (1.40 g, 97%). 1H NMR (DMSO-d6): δ 9.11 (s, 1H), 8.47 (s, 1H), 7.47-7.27 (m, 8H), 6.35 (s, 1H), 5.30 (t, J=5.6 Hz, 1H), 4.55 (d, J=5.6 Hz, 2H), 1.26 (s, 9H); MS (ESI) m/z: 399 (M+H+). excess LiAlH4 was quenched by adding ice Solvents were slowly removed the solid was filtered washed with EtOAc (200+100 mL) The filtrate was concentrated

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

Procedure: To a stirred solution of Example C (1.60 g, 3.63 mmol) in THF (200 mL) was added LiAlH4 powder (413 mg, 10.9 mmol) at −10° C. under N2. The mixture was stirred for 2 h and excess LiAlH4 was quenched by adding ice. The solution was acidified to pH=7 with dilute HCl. Solvents were slowly removed and the solid was filtered and washed with EtOAc (200+100 mL). The filtrate was concentrated to yield 1-{3-tert-butyl-1-[3-hydroxymethyl)phenyl]-1H-pyrazol-5-yl}-3-(4-chlorophenyl)urea (1.40 g, 97%). 1H NMR (DMSO-d6): δ 9.11 (s, 1H), 8.47 (s, 1H), 7.47-7.27 (m, 8H), 6.35 (s, 1H), 5.30 (t, J=5.6 Hz, 1H), 4.55 (d, J=5.6 Hz, 2H), 1.26 (s, 9H); MS (ESI) m/z: 399 (M+H+). excess LiAlH4 was quenched by adding ice Solvents were slowly removed the solid was filtered washed with EtOAc (200+100 mL) The filtrate was concentrated