Trifluoroacetic acid → HCID 68323920, compound

HRID 573685Notes

Reaction equation

HRID 573685 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][C:13]([CH3:36])=[CH:14][C:15]=3[N:17](COCC[Si](C)(C)C)[S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[C:23]([Cl:27])[CH:22]=3)(=[O:20])=[O:19])[S:10][CH:9]=2)[CH:5]=[CH:6][CH:7]=1.C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC(C)([O-])C.[Na+].[NH:89]1[CH2:93][CH2:92][CH2:91][CH2:90]1.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.C(Cl)Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Cl:27][C:23]1[CH:22]=[C:21]([S:18]([NH:17][C:15]2[CH:14]=[C:13]([CH3:36])[N:12]=[C:11]3[S:10][CH:9]=[C:8]([C:4]4[CH:5]=[CH:6][CH:7]=[C:2]([N:89]5[CH2:93][CH2:92][CH2:91][CH2:90]5)[CH:3]=4)[C:16]=23)(=[O:20])=[O:19])[CH:26]=[CH:25][CH:24]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acidHCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68380758HCID 68380758, compound

Product 1

HCID 68323920HCID 68323920, compoundYield 26.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of N-[3-(3-bromophenyl)-6-methylthieno[2,3-b]pyridin-4-yl]-3-chloro-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)benzenesulfonamide (Description 54) (960 mg, 1.538 mmol), BINAP (57.5 mg, 0.092 mmol), Pd2(dba)3 (28.2 mg, 0.031 mmol) and sodium tert-butoxide (443 mg, 4.61 mmol) in toluene (10 mL) was added pyrrolidine (0.254 mL, 3.08 mmol) and the mixture heated at 120° C. for ca. 2 h. After cooling to RT, the mixture was passed through celite, washed with DCM (ca. 20 mL×5) and the filtrate concentrated. The residue was purified by normal phase chromatography, eluting with 0-50% ethyl acetate in cyclohexane to give a residue which was subsequently taken-up in DCM (5 mL) and TFA (2.37 mL, 30.8 mmol) added. The mixture was stirred at RT overnight (ca. 16 h) and was then quenched with NaHCO3 solution (ca. 50 mL) and extracted with DCM (30 mL×3). The combined organics were dried and concentrated and the residue purified by normal phase chromatography, eluting with a gradient of 0-100% ethyl acetate in cyclohexane and then further purified by MDAP (basic conditions). Final purification by normal phase chromatography, eluting with 0-100% ethyl acetate in DCM, afforded the title compound (197 mg). LCMS (A) m/z: 484 [M+1]+, Rt 1.53 min (acidic).

Workup

  1. temperatureAfter cooling to RT
  2. washwashed with DCM (ca. 20 mL×5)
  3. concentrationthe filtrate concentrated
  4. customThe residue was purified by normal phase chromatography
  5. washeluting with 0-50% ethyl acetate in cyclohexane
  6. customto give a residue which
  7. customwas then quenched with NaHCO3 solution (ca. 50 mL)
  8. extractionextracted with DCM (30 mL×3)
  9. customThe combined organics were dried
  10. concentrationconcentrated
  11. customthe residue purified by normal phase chromatography
  12. washeluting with a gradient of 0-100% ethyl acetate in cyclohexane
  13. customfurther purified by MDAP (basic conditions)
  14. customFinal purification by normal phase chromatography
  15. washeluting with 0-100% ethyl acetate in DCM

Sources & evidence

ORD record
ord-2211bd3da9ff4721a5b41564ff413d76
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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