Sodium Thiosulfate → 5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde

HRID 334469ノート

反応式

HRID 334469 の反応式
[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH2:11][OH:12])=[N:9][N:8]([C:13]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:5]2=[N:6][CH:7]=1.[K+].[Br-].[O-]Cl.[Na+].[O-]S([O-])(=S)=O.[Na+].[Na+]>C(Cl)Cl.O.CC1(C)N([O])C(C)(C)CCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:10]([CH:11]=[O:12])=[N:9][N:8]([C:13]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:5]2=[N:6][CH:7]=1

参加物

8

反応物 4

HCID 24477Sodium ThiosulfateHCID 253877Potassium BromideHCID 23665760Sodium HypochloriteHCID 86701061(5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanol

生成物 1

HCID 867010605-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde収率 80.7%

試薬・触媒・溶媒 3

HCID 2724126Tempo触媒HCID 962Water溶媒3 回HCID 6344Dichloromethane溶媒

反応条件

温度
0 °C

実験手順

To a solution of (5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridin-3-yl)methanol (XXIII) (4.05 Kg, 8.6 mol) in DCM (97 L) was added a solution of KBr (205 g, 1.72 mol) in water (4 L). The solution was cooled to 0° C. before adding TEMPO (107.5 g, 688 mmol) and stirring for 30 min. To this solution was added a solution of KHCO3 (10.8 Kg, 107.4 mol) and aqueous 7% NaClO (13.4 L) in water (40 L). The reaction was stirred at 0° C. for 18 hours. A solution of Na2S2O3*5H2O (1.4 Kg, 5.7 mol) in water (9.1 L) was added dropwise to the reaction at 0° C. and stirred for 30 min. The aqueous layer was then separated and washed with DCM (48 L). The combined organic phases were washed with aqueous 25% NaCl (48 L), dried over Na2SO4, filtered and concentrated under vacuum. The residue was co-evaporated with 3×MeOH (20 L) and the solid was washed with 2×n-heptane (8 L). The solid was dried under vacuum at 45° C. to give 5-bromo-1-trityl-1H-pyrazolo[3,4-b]pyridine-3-carbaldehyde (XXIV) (3.25 Kg, 6.94 mol, 92.3% purity, 80.6% assay yield). 1H NMR (CDCl3, 400 MHz) δ ppm 7.19 (d, J=6 Hz, 5H), 7.22-7.34 (m, 10H), 8.28 (d, J=2.4 Hz, 1H), 8.70 (d, J=2.4 Hz, 1H), 10.07 (s, 1H); ESIMS found C26H18BrN3O m/z 490.0 (M+Na).

後処理

  1. stirringThe reaction was stirred at 0° C. for 18 hours
  2. stirringstirred for 30 min
  3. customThe aqueous layer was then separated
  4. washwashed with DCM (48 L)
  5. washThe combined organic phases were washed with aqueous 25% NaCl (48 L)
  6. dry with materialdried over Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. washthe solid was washed with 2×n-heptane (8 L)
  10. customThe solid was dried under vacuum at 45° C.

出典と根拠

ORDレコード
ord-09bfdac3d0494643b89ee08309a1ec10
出典データセット
uspto-grants-2014_11
特許番号
US08883822B2

反応ノート

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