Sodium Hydroxide → tert-butyl 9-[2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]-2,9-diazaspiro[5.5]undecane-2-carboxylate

HRID 1035796ノート

反応式

HRID 1035796 の反応式
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:33][CH2:32][C:19]5([CH2:24][N:23]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:22][CH2:21][CH2:20]5)[CH2:18][CH2:17]4)=[N:12][N:11]3[C:34]=2[C:35]2[CH:40]=[CH:39][N:38]=[C:37]3[N:41](S(C4C=CC(C)=CC=4)(=O)=O)[CH:42]=[CH:43][C:36]=23)=[CH:4][CH:3]=1.[OH-].[Na+]>CO.O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[N:9]=[C:10]3[CH:15]=[CH:14][C:13]([N:16]4[CH2:17][CH2:18][C:19]5([CH2:24][N:23]([C:25]([O:27][C:28]([CH3:29])([CH3:30])[CH3:31])=[O:26])[CH2:22][CH2:21][CH2:20]5)[CH2:32][CH2:33]4)=[N:12][N:11]3[C:34]=2[C:35]2[CH:40]=[CH:39][N:38]=[C:37]3[NH:41][CH:42]=[CH:43][C:36]=23)=[CH:6][CH:7]=1

参加物

5

反応物 2

HCID 14798Sodium HydroxideHCID 58046371HCID 58046371、化合物

生成物 1

HCID 58046358tert-butyl 9-[2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]-2,9-diazaspiro[5.5]undecane-2-carboxylate

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 8028Tetrahydrofuran溶媒

実験手順

The tert-butyl 9-{2-(4-fluorophenyl)-3-[1-(4-methylphenylsulphonyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]imidazo[1,2-b]pyridazin-6-yl}-2,9-diazaspiro[5.5]undecane-2-carboxylate obtained in step 5.1 is dissolved in 3 ml of a mixture of methanol and tetrahydrofuran (2/1) and is treated using 0.09 ml (0.54 mmol) of a 6N aqueous solution of sodium hydroxide at 60° C. for 1 and a half hours. The solvent is evaporated under reduced pressure and the residue taken up in 3 ml of water. The product is extracted 2 times with 3 ml of dichloromethane. The organic phase is dried over sodium sulphate and the solvent is removed by evaporation under reduced pressure. The residue obtained is then purified by chromatography on a silica gel column (4 g) by eluting with a gradient of dichloromethane, methanol and aqueous ammonia (of 95/5/05 to 90/10/1) in order to give 0.06 g of tert-butyl 9-[2-(4-fluorophenyl)-3-(1H-pyrrolo[2,3-b]pyridin-4-yl)imidazo[1,2-b]pyridazin-6-yl]-2,9-diazaspiro[5.5]undecane-2-carboxylate after crystallization in 10 ml of acetonitrile, filtration and drying.

後処理

  1. additionis treated
  2. customat 60° C.
  3. customfor 1 and a half hours
  4. customThe solvent is evaporated under reduced pressure
  5. extractionThe product is extracted 2 times with 3 ml of dichloromethane
  6. dry with materialThe organic phase is dried over sodium sulphate
  7. customthe solvent is removed by evaporation under reduced pressure
  8. customThe residue obtained
  9. customis then purified by chromatography on a silica gel column (4 g)
  10. washby eluting with a gradient of dichloromethane, methanol and aqueous ammonia (of 95/5/05 to 90/10/1) in order

出典と根拠

ORDレコード
ord-f1d84c779d024991acf4b6d5a494caf8
出典データセット
uspto-grants-2013_10
特許番号
US08546395B2

反応ノート

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