Sodium Carbonate → HCID 59700037, compound

HRID 901433Notes

Reaction equation

HRID 901433 reaction equation
Cl.Br[C:3]1[CH:4]=[C:5]2[C:11]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]4[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]4)=[CH:14][CH:13]=3)=[CH:10][NH:9][C:6]2=[N:7][CH:8]=1.[CH3:28][O:29][C:30]1[CH:31]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:33]=[CH:34][C:35]=1[O:36]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>[CH3:28][O:29][C:30]1[CH:31]=[C:32]([C:3]2[CH:4]=[C:5]3[C:11]([C:12]4[CH:17]=[CH:16][C:15]([O:18][CH2:19][CH2:20][CH2:21][N:22]5[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]5)=[CH:14][CH:13]=4)=[CH:10][NH:9][C:6]3=[N:7][CH:8]=2)[CH:33]=[CH:34][C:35]=1[OH:36]

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 516892Sodium BicarbonateHCID 67061226HCID 67061226, compoundHCID 670612332-[3-Methoxy-4-[(4-methoxyphenyl)methoxy]phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 59700037HCID 59700037, compoundYield 8.3%

Reagents, catalysts & solvents 3

HCID 178418903HCID 178418903, compoundCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

100 mg (0.24 mmol) of 5-bromo-3-[4-(3-piperidin-1-yl-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridine hydrochloride, 120 mg (0.33 mmol) of 2-[3-Methoxy-4-(4-methoxy-benzyloxy)-phenyl]-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane and 10 mg (5 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 three times with dichloromethane and the combined organic phases were dried over sodium sulfate and evaporated. The crude product was purified by flash chromatography on amine functionalized silica gel (ISCO RediSep® amine column) using a gradient of ethyl acetate in hexanes. The resulting intermediate was dissolved in 30 ml of dichloromethane and 750 mg (1.06 mmol) of PS-thiophenol (Argonaut Technologies) was added. To this was added 1.5 ml of trifluoroacetic acid and the mixture was stirred at room temperature for 2 hours. The resin was filtered off and washed with dichloromethane. The filtrate was washed with a saturated aqueous solution of sodium bicarbonate, dried over sodium sulfate and evaporated. The residue was triturated with 20 ml of dichloromethane and dried by suction to afford 9 mg (20 μmol, 8% yield) of 2-methoxy-4-{3-[4-(3-piperidin-1-yl-propoxy)-phenyl]-1H-pyrrolo[2,3-b]pyridin-5-yl}-phenol as a beige powder. 1H-NMR (d6-DMSO) δ: 11.83 [1H] d, 9.06 [1H] s, 8.50 [1H] d, 8.28 [1H] d, 7.76 [1H], 7.67 [2H] d(m), 7.25 [1H] d, 7.12 [1H] dd, 7.01 [2H] d(m), 6.88 [1H] d, 4.02 [2H] t, 3.87 [3H] s, 2.39 [2H] t, 2.34 [4H] (m),br, 1.88 [2H] t, 1.50 [4H] qui, 1.38 [2H] (m). MS, m/z: 458 [MH+].

Workup

  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 three times with dichloromethane
  4. dry with materialthe combined organic phases were dried over sodium sulfate
  5. customevaporated
  6. customThe crude product was purified by flash chromatography on amine functionalized silica gel (ISCO RediSep® amine column)
  7. dissolutionThe resulting intermediate was dissolved in 30 ml of dichloromethane
  8. addition750 mg (1.06 mmol) of PS-thiophenol (Argonaut Technologies) was added
  9. additionTo this was added 1.5 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. dry with materialdried over sodium sulfate
  14. customevaporated
  15. customThe residue was triturated with 20 ml of dichloromethane
  16. customdried by suction

Sources & evidence

ORD record
ord-829c7b7ba5d94e06aa384d386db6f3e1
Source dataset
uspto-grants-2008_04
Patent number
US07361763B2

Reaction notes

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