Sodium Carbonate → HCID 136339761、化合物

HRID 1171140ノート

反応式

HRID 1171140 の反応式
I[N:2]1[C:6]2[N:7]=[C:8]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)[CH2:9][NH:10][C:5]=2[CH:4]=[CH:3]1.[CH3:18][O:19][C:20]1[CH:21]=[C:22](B2OC(C)(C)C(C)(C)O2)[CH:23]=[CH:24][C:25]=1[O:26]CC1C=CC(OC)=CC=1.C(=O)([O-])[O-].[Na+].[Na+].C(=O)(O)[O-].[Na+]>Cl[Pd-2](Cl)(P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)P(C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.ClCCl.C(#N)C>[CH3:18][O:19][C:20]1[CH:21]=[C:22]([N:2]2[C:6]3[N:7]=[C:8]([C:11]4[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=4)[CH2:9][NH:10][C:5]=3[CH:4]=[CH:3]2)[CH:23]=[CH:24][C:25]=1[OH:26]

参加物

8

反応物 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 670612332-[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 136405680HCID 136405680、化合物

生成物 1

HCID 136339761HCID 136339761、化合物収率 18%

試薬・触媒・溶媒 3

HCID 178418903HCID 178418903、化合物触媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

84 mg (0.25 mmol) of 4-(5-iodo-1H-pyrrolo[2,3-b]pyrazin-3-yl)-phenol, 120 mg (0.33 mmol) of 2-[3-methoxy-4-(4-methoxy-benzyloxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane and 15 mg (8 mol %) of dichlorobis(triphenylphosphino)palladium(II) were placed in a vial and 1.5 ml of acetonitrile and 1.5 ml of a 2 M aqueous solution of sodium carbonate were added. The mixture was irradiated in a Personal Chemistry® microwave reactor to 165° C. for 1200 sec. The resulting mixture was distributed between dichloromethane and a saturated aqueous solution of sodium bicarbonate. The aqueous layer was extracted twice with dichloromethane and the combined organic phases were dried over sodium sulfate and evaporated. The crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes. The resulting intermediate was dissolved in 120 ml of dichloromethane and 1.5 g (2.12 mmol) of PS-thiophenol (Argonaut Technologies) was added. To this was added 2 ml of trifluoroacetic acid and the mixture stirred at room temperature for 1 hour. The resin was filtered off and washed with dichloromethane. The filtrate was washed with a saturated aqueous solution of sodium bicarbonate. The phases were separated and the aqueous layer extracted twice with ethyl acetate. All organic phases were combined, dried over sodium sulfate and evaporated. The residue was heated up with acetonitrile, cooled down to room temperature and the supernatant was removed. The residue was dried in vacuo to afford 15 mg (45 μmol, 18% yield) of 4-{5-[3-methoxy-4hydroxyphenyl]-1H-pyrrolo[2,3-b]pyrazin-3-yl}-phenol as a beige powder. 1H-NMR (d6-DMSO) δ: 12.06 [1H] d, 9.35 [1H] s, 9.30 [1H] s, 8.83 [1H] s, 8.20 [1H] d, 8.12 [2H] d (m), 7.75 [1H] d, 7.65 [1H] dd, 6.93 [1H] d, 6.85 [2H] d (m), 3.91 [3H] s. MS, m/z: 334 [MH+].

後処理

  1. additionwere added
  2. customThe mixture was irradiated in a Personal Chemistry® microwave reactor to 165° C. for 1200 sec
  3. extractionThe aqueous layer was extracted twice with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customevaporated
  6. customThe crude was purified by flash chromatography on silica gel using a gradient of ethyl acetate in hexanes
  7. dissolutionThe resulting intermediate was dissolved in 120 ml of dichloromethane
  8. addition1.5 g (2.12 mmol) of PS-thiophenol (Argonaut Technologies) was added
  9. additionTo this was added 2 ml of trifluoroacetic acid
  10. filtrationThe resin was filtered off
  11. washwashed with dichloromethane
  12. washThe filtrate was washed with a saturated aqueous solution of sodium bicarbonate
  13. customThe phases were separated
  14. extractionthe aqueous layer extracted twice with ethyl acetate
  15. dry with materialdried over sodium sulfate
  16. customevaporated
  17. temperatureThe residue was heated up with acetonitrile
  18. temperaturecooled down to room temperature
  19. customthe supernatant was removed
  20. customThe residue was dried in vacuo

出典と根拠

ORDレコード
ord-b121cb67abd040b4b0516eb14cdb1042
出典データセット
uspto-grants-2010_11
特許番号
US07829558B2

反応ノート

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