O-(2,4,6-Trimethylbenzenesulfonyl)hydroxylamine → HCID 86662453, compound

HRID 2188980Notes

Reaction equation

HRID 2188980 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]([CH3:13])[C:10]([C:14]2[CH:19]=[CH:18][N:17]=[N:16][CH:15]=2)=[CH:9][C:4]=1[C:5]([O:7][CH3:8])=[O:6].[C:20]1([CH3:33])[CH:25]=[C:24]([CH3:26])[CH:23]=[C:22]([CH3:27])[C:21]=1[S:28]([O:31][NH2:32])(=[O:30])=[O:29]>ClCCl>[CH3:27][C:22]1[CH:23]=[C:24]([CH3:26])[CH:25]=[C:20]([CH3:33])[C:21]=1[S:28]([O-:31])(=[O:30])=[O:29].[NH2:32][N+:17]1[CH:18]=[CH:19][C:14]([C:10]2[CH:9]=[C:4]([C:5]([O:7][CH3:8])=[O:6])[C:3]([O:2][CH3:1])=[CH:12][C:11]=2[CH3:13])=[CH:15][N:16]=1

Participants

4

Reactant 2

HCID 11830845O-(2,4,6-Trimethylbenzenesulfonyl)hydroxylamineHCID 66763792HCID 66763792, compound

Product 1

HCID 86662453HCID 86662453, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Methyl 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-2-(4-fluorophenyl)pyrazolo[1,5-h]pyridazin-5-yl)-2-methoxy-4-methylbenzoate and methyl 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-2-(4-fluorophenyl)pyrazolo[1,5-h]pyridazin-4-yl)-2-methoxy-4-methylbenzoate. Part A: To a cooled solution (0° C., ice bath) containing methyl 2-methoxy-4-methyl-5-(pyridazin-4-yl)benzoate (0.16 g, 0.66 mmol) and dichloromethane (3 mL) was added O-(mesitylsulfonyl)hydroxylamine (0.32 g, 0.90 mmol) in dichloromethane (3 mL) quickly, dropwise. The solution was maintained at 0° C. for 5 min, removed from the cooling bath and maintained at ambient temperature for 5 h. The solution was concentrated to afford 1-amino-4-(4-methoxy-5-(methoxycarbonyl)-2-methylphenyl)pyridazin-1-ium 2,4,6-trimethylbenzenesulfonate as a foam (274 MH+). Part B: The product thus obtained in part A was suspended in THF (2.0 mL). tert-butyl 3-(4-fluorophenyl)propioloyl(methyl)carbamate (0.17 g, 0.60 mmol) was added and the suspension cooled to −78° C. (dry Ice/acetone bath). DBU (0.27 g, 1.8 mmol) in THF (1.0 mL) was added dropwise over 2 min. The mixture was left in the cooling bath for 20 min, then removed from cooling and allowed to proceed for 20 h at ambient temperature. The mixture was filtered and concentrated. Purification on silica gel (20-80% ethyl acetate/hexanes, 60 min gradient) afforded methyl 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-2-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-5-yl)-2-methoxy-4-methylbenzoate and methyl 5-(3-(tert-butoxycarbonyl(methyl)carbamoyl)-2-(4-fluorophenyl)pyrazolo[1,5-b]pyridazin-4-yl)-2-methoxy-4-methylbenzoate as separate regioisomers.

Workup

  1. customremoved from the cooling bath
  2. temperaturemaintained at ambient temperature for 5 h
  3. concentrationThe solution was concentrated

Sources & evidence

ORD record
ord-4dac6c66d8b948638be1f5b33ddf95e4
Source dataset
uspto-grants-2012_12
Patent number
US08324212B2

Reaction notes

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