Formaldehyde → 4-{4-Chloro-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

HRID 46255ノート

反応式

HRID 46255 の反応式
[NH:1]1[CH2:4][CH:3]([N:5]2[C:9]([C:10]3[CH:33]=[C:32]([Cl:34])[CH:31]=[CH:30][C:11]=3[O:12][C:13]3[C:18]([F:19])=[CH:17][C:16]([S:20]([NH:23][C:24]4[S:28][N:27]=[CH:26][N:25]=4)(=[O:22])=[O:21])=[C:15]([F:29])[CH:14]=3)=[CH:8][CH:7]=[N:6]2)[CH2:2]1.Cl[CH2:36]Cl.C=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(C(C)=O)C(C)C.C(O)(=O)C.O.C(OCC)(=O)C>[Cl:34][C:32]1[CH:31]=[CH:30][C:11]([O:12][C:13]2[C:18]([F:19])=[CH:17][C:16]([S:20]([NH:23][C:24]3[S:28][N:27]=[CH:26][N:25]=3)(=[O:21])=[O:22])=[C:15]([F:29])[CH:14]=2)=[C:10]([C:9]2[N:5]([CH:3]3[CH2:2][N:1]([CH3:36])[CH2:4]3)[N:6]=[CH:7][CH:8]=2)[CH:33]=1

参加物

7

反応物 4

HCID 712Formaldehyde2 回HCID 6344DichloromethaneHCID 5049666Sodium triacetoxyborohydride2 回HCID 46841215NaV1.7 Blocker-801

生成物 1

HCID 468414994-{4-Chloro-2-[1-(1-methylazetidin-3-yl)-1H-pyrazol-5-yl]phenoxy}-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide

試薬・触媒・溶媒 2

HCID 8857Ethyl Acetate溶媒HCID 86643822Methyl isobutyl ketone acetic acid water溶媒

実験手順

4-[2-(1-azetidin-3-yl-1H-pyrazol-5-yl)-4-chlorophenoxy]-2,5-difluoro-N-1,2,4-thiadiazol-5-ylbenzenesulfonamide (Example 801, 54 mg, 0.1 mmol) was stirred with dichloromethane (2 mL) methanol (0.2 mL) and 37% w/v aqueous formaldehyde solution (0.025 mL, 0.34 mmol) at room temperature for 15 minutes. Sodium triacetoxyborohydride (68 mg, 0.32 mmol) was added at the reaction stirred at room temperature for 18 hours. 37% wt/vol aqueous formaldehyde solution (0.025 mL, 0.34 mmol) was added and the reaction stirred for 15 minutes then sodium triacetoxyborohydride (68 mg, 0.32 mmol) was added at the reaction stirred at room temperature for 3 hours. The mixture was evaporated and the residue dissolved in ethyl acetate (20 mL) and washed with saturated aqueous sodium bicarbonate solution (2×10 ml) and saturated aqueous sodium chloride solution (2×10 ml). The organic layer was separated, dried over sodium sulphate, filtered and evaporated to give a solid. The solid was suspended in methyl isobutyl ketone:acetic acid:water 2:1:1 and eluted through a silica column (5 g) with methyl isobutyl ketone:acetic acid:water 2:1:1. The appropriate fractions were combined and concentrated in vacuo to give a film. This was scratched with ethyl acetate then diethyl ether and dried in vacuo to give the title compound as a white solid. Yield 30 mg. 54%.

後処理

  1. customat room temperature
  2. customfor 15 minutes
  3. stirringthe reaction stirred for 15 minutes
  4. stirringstirred at room temperature for 3 hours
  5. customThe mixture was evaporated
  6. dissolutionthe residue dissolved in ethyl acetate (20 mL)
  7. washwashed with saturated aqueous sodium bicarbonate solution (2×10 ml) and saturated aqueous sodium chloride solution (2×10 ml)
  8. customThe organic layer was separated
  9. dry with materialdried over sodium sulphate
  10. filtrationfiltered
  11. customevaporated
  12. customto give a solid
  13. washeluted through a silica column (5 g) with methyl isobutyl ketone:acetic acid:water 2:1:1
  14. concentrationconcentrated in vacuo
  15. customto give a film
  16. dry with materialdiethyl ether and dried in vacuo

出典と根拠

ORDレコード
ord-270c91e60bd34891ba40fedd5cd42ef8
出典データセット
uspto-grants-2013_09
特許番号
US08541588B2

反応ノート

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