Sodium Carbonate → HCID 68110325, compound

HRID 2369409Notes

Reaction equation

HRID 2369409 reaction equation
Br[C:2]1[C:10]2[C:9]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[S:4][C:3]=1[CH2:21][CH3:22].B(O)O.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[C:45](=[O:48])([O-])[O-].[Na+].[Na+].[C:51]1([CH3:57])[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1.O>O.CC([O-])=O.CC([O-])=O.[Pd+2]>[O:48]1[C:45]2[CH:56]=[CH:55][CH:54]=[CH:53][C:52]=2[CH:51]=[C:57]1[C:2]1[C:10]2[C:9]([NH:11][CH:12]3[CH2:17][CH2:16][CH:15]([N:18]([CH3:20])[CH3:19])[CH2:14][CH2:13]3)=[N:8][CH:7]=[N:6][C:5]=2[S:4][C:3]=1[CH2:21][CH3:22]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 61668Boronic AcidHCID 22272177Toluene waterHCID 68110300HCID 68110300, compound

Product 1

HCID 68110325HCID 68110325, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Procedure

A solution of 4-N-[5-bromo-6-ethylthieno[2,3-d]pyrimidin-4-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (1 g, 2.61 mmol, 1.00 equiv) in toluene/H2O (30/10 mL) was added 1-benzofuran-2-yl)boronic acid (970 mg, 5.99 mmol, 2.30 equiv), Pd(OAc)2 (70 mg, 0.31 mmol, 0.12 equiv), PPh3 (240 mg, 0.92 mmol, 0.35 equiv) and sodium carbonate (940 mg, 8.87 mmol, 3.40 equiv) subsequently under nitrogen. The resulting solution was heated to reflux for 4 hr and cooled to room temperature. The resulting solution was diluted with 50 mL of H2O and extracted with 3×80 mL of ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous sodium sulfate and concentrated under vacuum. The crude product (500 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU): Column, SunFire Prep C18, 19*150 mm 5 um; mobile phase, water with 0.05% TFA and CH3CN (10% CH3CN up to 30% in 14 min); Flow rate, 20 mL/min; UV detection at 254/220 nm. The product-containing fractions were collected and partially evaporated to remove water and CH3CN under reduced pressure. The residue was neutralized with 2 M aqueous NaOH solution and extracted with DCM, dried over Na2SO4 and concentrated under reduced pressure to give the corresponding 4-N-[5-(1-benzofuran-2-yl)-6-ethylthieno[2,3-d]pyrimidin-4-yl]-1-N,1-N-dimethylcyclohexane-1,4-diamine (130 mg) as yellow semi-solid. MS (ES, m/z): 421 [M+H]+. 1H NMR (300 Hz, CDCl3): δ 8.45 (s, 1H), 7.71-7.68 (d, 1H), 7.57-7.54 (d, 1H), 7.45-7.36 (m, 2H), 6.85 (s, 1H), 5.44-5.42 (d, 1H), 4.03-3.93 (m, 1H) 2.99-2.91 (dd, 2H), 2.30 (s, 6H) 2.23-2.10 (m, 4H), 2.02-1.85 (m, 3H), 1.46-1.31 (m, 5H), 0.92-0.89 (dd, 2H).

Workup

  1. temperatureThe resulting solution was heated
  2. temperatureto reflux for 4 hr
  3. extractionextracted with 3×80 mL of ethyl acetate
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under vacuum
  7. customThe crude product (500 mg) was purified by Prep-HPLC with the following conditions (SHIMADZU)
  8. customThe product-containing fractions were collected
  9. custompartially evaporated
  10. customto remove water and CH3CN under reduced pressure
  11. extractionextracted with DCM
  12. dry with materialdried over Na2SO4
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-91d7aee78d3c460c88752610fb019958
Source dataset
uspto-grants-2014_04
Patent number
US08703941B2

Reaction notes

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