Potassium Carbonate → tert-butyl 4-((4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl)piperidine-1-carboxylate

HRID 2241404

反応式

HRID 2241404 の反応式
[CH2:1]=[C:2]1[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]1.B1C2CCCC1CCC2.[CH3:24][O:25][C:26]1[CH:51]=[CH:50][C:29]([CH2:30][N:31]2[C:35]3=[N:36][CH:37]=[CH:38][C:39]([O:40][C:41]4[CH:46]=[CH:45][C:44]([NH2:47])=[CH:43][C:42]=4[F:48])=[C:34]3[C:33](I)=[N:32]2)=[CH:28][CH:27]=1.C(=O)([O-])[O-].[K+].[K+].[OH-].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O>[NH2:47][C:44]1[CH:45]=[CH:46][C:41]([O:40][C:39]2[CH:38]=[CH:37][N:36]=[C:35]3[N:31]([CH2:30][C:29]4[CH:50]=[CH:51][C:26]([O:25][CH3:24])=[CH:27][CH:28]=4)[N:32]=[C:33]([CH2:1][CH:2]4[CH2:7][CH2:6][N:5]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[CH2:4][CH2:3]4)[C:34]=23)=[C:42]([F:48])[CH:43]=1

参加物

9

反応物 5

HCID 11430Potassium CarbonateHCID 14798Sodium HydroxideHCID 789669-Borabicyclo(3.3.1)nonaneHCID 27568081-Boc-4-MethylenepiperidineHCID 672210033-Fluoro-4-((3-iodo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)oxy)aniline

生成物 1

HCID 68517133tert-butyl 4-((4-(4-amino-2-fluorophenoxy)-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl)piperidine-1-carboxylate

試薬・触媒・溶媒 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)触媒HCID 962Water溶媒2 回HCID 6228Dimethylformamide溶媒

反応条件

温度
72 °C

実験手順

To a 10 mL reaction flask was added tert-butyl 4-methylenepiperidine-1-carboxylate (81 mg, 0.411 mmol) and was purged with N2(g) three times. 9-BBN (0.821 ml, 0.411 mmol) was added and the clear solution refluxed (72° C.) for 1 hour. The reaction was cooled to ambient temperature and then added directly to a mixture of 4-(1-(4-methoxybenzyl)-3-iodo-1H-pyrazolo[3,4-b]pyridin-4-yloxy)-3-fluorobenzenamine (181 mg, 0.370 mmol; prepared as in Example 7, Step B), 1,1′-bis(diphenylphosphino)ferrocenedichloropalladium(II) (10.1 mg, 0.0123 mmol) and potassium carbonate (68.1 mg, 0.493 mmol) in DMF:H2O (1 mL:0.1 mL). The dark orange mixture was stirred at 60° C. for 6 hours, then cooled to ambient temperature and poured into water. The pH was adjusted to 11 with 1N NaOH, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and evaporated. The residue was purified by silica gel column chromatography (Biotage 25M) eluting with 3% MeOH/CH2Cl2 to afford the desired product. Yield: 25 mg, 11%. LRMS (APCI pos) m/e 562.1 (M+H).

後処理

  1. customTo a 10 mL reaction flask
  2. customwas purged with N2(g) three times
  3. temperatureThe reaction was cooled to ambient temperature
  4. temperaturecooled to ambient temperature
  5. extractionthe aqueous layer was extracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over Na2SO4
  8. customevaporated
  9. customThe residue was purified by silica gel column chromatography (Biotage 25M)
  10. washeluting with 3% MeOH/CH2Cl2

出典と根拠

ORDレコード
ord-8a0d7137042b49bfbf0a8e8a6fc39746
出典データセット
uspto-grants-2010_05
特許番号
US07723330B2

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