Tetrahydrofuran → hydroxy-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid

HRID 886585노트

반응식

HRID 886585 반응식
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[C:9]1[C:17]2[C:12](=[N:13][CH:14]=[C:15](B3OC(C)(C)C(C)(C)O3)[CH:16]=2)[N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[N:10]=1.Br[C:36]1[CH:37]=[C:38]([CH:44]=[CH:45][CH:46]=1)[CH:39]([OH:43])[C:40]([OH:42])=[O:41].C1COCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].C(#N)C>[OH:43][CH:39]([C:38]1[CH:44]=[CH:45][CH:46]=[C:36]([C:15]2[CH:16]=[C:17]3[C:9]([C:4]4[CH:5]=[CH:6][CH:7]=[CH:8][C:3]=4[O:2][CH3:1])=[N:10][N:11]([CH2:27][O:28][CH2:29][CH2:30][Si:31]([CH3:34])([CH3:33])[CH3:32])[C:12]3=[N:13][CH:14]=2)[CH:37]=1)[C:40]([OH:42])=[O:41]

참가 물질

7

반응물 4

HCID 8028TetrahydrofuranHCID 10340Sodium CarbonateHCID 27570282-(3-Bromophenyl)-2-hydroxyacetic acidHCID 598360923-(2-methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxy-methyl)-1H-pyrazolo[3,4-b]pyridine

생성물 1

HCID 59825066hydroxy-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid수율 70.4%

시약·촉매·용매 2

HCID 53485975CID 53485975촉매HCID 6342Acetonitrile용매

실험 절차

To a mixture of 3-(2-Methoxy-phenyl)-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridine (500 mg, 1.04 mmol) and 3-bromomandelic acid (288 mg, 1.25 mmol) in a 20 mL microwave reaction flask was added THF (3 mL), acetonitrile (3 mL) and sodium carbonate (3 mL, 1 N aqueous solution, 3 mmol). The mixture was purged with nitrogen for 1 min. dichloro[1,1′-bis(diphenylphoshino)ferrocene]palladium(II) dichloromethane adduct (73 mg, 89 μmol) was added and the purging continued for another minute. The flask was sealed and irradiated in a microwave reactor to 120° C. for 20 min. The reaction mixture was partitioned between aqueous saturated sodium chloride and ethyl acetate (15 mL:15 mL). The aqueous layer was extracted with ethyl acetate (10 mL×2). The combined organic layers were washed with brine, dried over sodium sulfate and evaporated. The resulting crude was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane to afford hydroxy-{3-[3-(2-methoxy-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-b]pyridin-5-yl]-phenyl}-acetic acid as a yellow solid (370 mg, 67% yield). MS: m/z 506 (M+H+).

후처리

  1. customin a 20 mL microwave reaction flask
  2. additionwas added
  3. customThe flask was sealed
  4. customirradiated in a microwave reactor to 120° C. for 20 min
  5. customThe reaction mixture was partitioned between aqueous saturated sodium chloride and ethyl acetate (15 mL:15 mL)
  6. extractionThe aqueous layer was extracted with ethyl acetate (10 mL×2)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. customevaporated
  10. customThe resulting crude was purified by flash chromatography on silica gel using a gradient of methanol in dichloromethane

출처 및 근거

ORD 기록
ord-4793ad29420040a0ab05a172d9162291
출처 데이터셋
uspto-grants-2012_08
특허 번호
US08242280B2

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