Trifluoroacetic acid → HCID 68323820, compound

HRID 573687Notes

Reaction equation

HRID 573687 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[C:16]3[C:11](=[N:12][C:13]([CH3:35])=[CH:14][C:15]=3[N:17](COCC[Si](C)(C)C)[S:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)(=[O:20])=[O:19])[S:10][C:9]=2[C:36]2[CH:37]=[N:38][N:39](COCC[Si](C)(C)C)[CH:40]=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:101]1[CH2:105][CH2:104][CH2:103][CH2:102]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]>[CH3:35][C:13]1[N:12]=[C:11]2[S:10][C:9]([C:36]3[CH:37]=[N:38][NH:39][CH:40]=3)=[C:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([N:101]4[CH2:105][CH2:104][CH2:103][CH2:102]4)[CH:3]=3)[C:16]2=[C:15]([NH:17][S:18]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)(=[O:20])=[O:19])[CH:14]=1

Participants

9

Reactant 5

HCID 6422Trifluoroacetic acid3×HCID 31268PyrrolidineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 68380825HCID 68380825, compound

Product 1

HCID 68323820HCID 68323820, compoundYield 35.5%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of N-{3-(3-bromophenyl)-6-methyl-2-[1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrazol-4-yl]thieno[2,3-b]pyridin-4-yl}-N-({[2-(trimethylsilyl)ethyl]oxy}methyl)benzenesulfonamide (Description 51) (485 mg, 0.617 mmol), BINAP (23.05 mg, 0.037 mmol), Pd2(dba)3 (11.30 mg, 0.012 mmol) and sodium tert-butoxide (178 mg, 1.851 mmol) in toluene (5 mL) was added pyrrolidine (0.102 mL, 1.234 mmol) and the mixture was 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 (0.475 mL, 6.17 mmol) added. The mixture was stirred at RT overnight (ca. 24 h). Extra TFA (0.475 mL, 6.17 mmol) was added and stirring continued at RT for ca. 4 h. Extra TFA (0.475 mL, 6.17 mmol) was added and stirring continued at RT overnight (ca. 20 h). The reaction mixture was then passed through SCX cartridge, eluting with MeOH (150 mL), then with 2M NH3 in MeOH (200 mL). The basic methanolic solution was concentrated and the residue purified by normal phase chromatography, eluting with 0-100% ethyl acetate in cyclohexane and then further purified by MDAP (acidic conditions) and then by MDAP (basic conditions), to afford the title compound (113 mg). LCMS (A) m/z: 516 [M+1]+, Rt 1.28 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. stirringstirring
  8. waitcontinued at RT for ca. 4 h
  9. stirringstirring
  10. waitcontinued at RT overnight
  11. custom(ca. 20 h)
  12. washeluting with MeOH (150 mL)
  13. concentrationThe basic methanolic solution was concentrated
  14. customthe residue purified by normal phase chromatography
  15. washeluting with 0-100% ethyl acetate in cyclohexane
  16. customfurther purified by MDAP (acidic conditions)

Sources & evidence

ORD record
ord-02ae638c5c4342318eb7adfc1ec1e2ed
Source dataset
uspto-grants-2015_05
Patent number
US09029545B2

Reaction notes

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