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

반응식

HRID 2241404 반응식
[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

참가 물질

9

반응물 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

생성물 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

시약·촉매·용매 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매HCID 962Water용매2회HCID 6228Dimethylformamide용매

반응 조건

온도
72 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-8a0d7137042b49bfbf0a8e8a6fc39746
출처 데이터셋
uspto-grants-2010_05
특허 번호
US07723330B2

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