Potassium Carbonate → (3R*,4S*)-tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-ylamino)-3-fluoropiperidine-1-carboxylate

HRID 2241421ノート

反応式

HRID 2241421 の反応式
[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10](I)=[N:9]2)=[CH:5][CH:4]=1.[NH2:29][C@@H:30]1[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])[CH2:32][C@@H:31]1[F:43].N1CCC[C@H]1C(O)=O.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[CH3:1][O:2][C:3]1[CH:28]=[CH:27][C:6]([CH2:7][N:8]2[C:12]3=[N:13][CH:14]=[CH:15][C:16]([O:17][C:18]4[CH:23]=[CH:22][C:21]([NH2:24])=[CH:20][C:19]=4[F:25])=[C:11]3[C:10]([NH:29][C@H:30]3[CH2:35][CH2:34][N:33]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])[CH2:32][C@H:31]3[F:43])=[N:9]2)=[CH:5][CH:4]=1

参加物

7

反応物 4

HCID 11430Potassium CarbonateHCID 145742L-ProlineHCID 11736104tert-butyl (3S,4R)-4-amino-3-fluoropiperidine-1-carboxylateHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

生成物 1

HCID 68516487(3R*,4S*)-tert-butyl 4-(1-(4-methoxybenzyl)-4-(4-amino-2-fluorophenoxy)-1H-pyrazolo[3,4-b]pyridin-3-ylamino)-3-fluoropiperidine-1-carboxylate

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
100 °C

実験手順

A mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (0.123 g, 0.25 mmol, prepared according to Example 7, Step B), ±(3S*,4R*)-tert-butyl 4-amino-3-fluoropiperidine-1-carboxylate (0.164 g, 0.750 mmol, prepared according to WO 2006/087543), copper(I)iodide (0.00952 g, 0.0500 mmol), (S)-pyrrolidine-2-carboxylic acid (0.0115 g, 0.100 mmol), K2CO3 (0.173 g, 1.25 mmol), and DMSO (1 mL) was stirred at 100° C. for 3 days. The reaction was partitioned between EtOAc and water. The phases were separated and the aqueous phase was re-extracted with EtOAc (5 mL). The combined organic phases were washed with water, dried (Na2SO4), filtered, and concentrated. The crude was purified by preparative TLC (1 mm thickness, Rf=0.56) eluting with 10% MeOH/CHCl3. LRMS (APCI+): m/z 581 (M+1) detected.

後処理

  1. customThe reaction was partitioned between EtOAc and water
  2. customThe phases were separated
  3. extractionthe aqueous phase was re-extracted with EtOAc (5 mL)
  4. washThe combined organic phases were washed with water
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude was purified by preparative TLC (1 mm thickness, Rf=0.56)
  9. washeluting with 10% MeOH/CHCl3

出典と根拠

ORDレコード
ord-fa827390172e43319ab2674ca9cc33b1
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

反応ノート

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