Trifluoroacetic acid → HCID 71656475, compound

HRID 877592Notes

Reaction equation

HRID 877592 reaction equation
Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[N:9]=2)=[C:4]([NH:16][CH:17]([CH3:19])[CH3:18])[CH:3]=1.[NH2:20][C:21]1[CH:29]=[CH:28][C:24]2[N:25]=[CH:26][S:27][C:23]=2[CH:22]=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+].C(O)(C(F)(F)F)=O>C1(C)C=CC=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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O.C(#N)C.CO>[S:27]1[C:23]2[CH:22]=[C:21]([NH:20][C:2]3[N:7]=[CH:6][C:5]([C:8]4[CH:13]=[CH:12][CH:11]=[C:10]([O:14][CH3:15])[N:9]=4)=[C:4]([NH:16][CH:17]([CH3:19])[CH3:18])[CH:3]=3)[CH:29]=[CH:28][C:24]=2[N:25]=[CH:26]1

Participants

11

Reactant 5

HCID 6422Trifluoroacetic acid4×HCID 682886-AminobenzothiazoleHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 89689777HCID 89689777, compound

Product 1

HCID 71656475HCID 71656475, compound

Reagents, catalysts & solvents 5

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 887MethanolSolvent2×HCID 962WaterSolvent4×HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
110 °C

Procedure

6′-Chloro-N-isopropyl-6-methoxy-[2,3′-bipyridin]-4′-amine (25 mg, 0.090 mmol), 6-aminobenzothiazole (20.28 mg, 0.135 mmol), BINAP (1.121 mg, 1.800 μmol), sodium tert-butoxide (26.0 mg, 0.270 mmol) were dissolved in Toluene (1 ml) in a sealed tube and thoroughly purged with N2 for 5 minutes. Pd2(dba)3 (3.3 mg, 3.6 μmol) was added and the reaction mass was once again purged with N2 for 5 minutes. The pressure tube was sealed and heated at 110° C. overnight. The reaction was cooled to rt and passed through a celite bed and washed with DCM. The filtrate was concentrated, dissolved in 10 mL water and extracted with DCM (3×8 mL). The combined organic layers were dried, concentrated and purified via preparative HPLC to afford Example 176. 1H NMR: 400 MHz, CD3OD: δ 1.33 (d, J=6.40 Hz, 6H), 3.74-3.80 (m, 1H), 3.99 (s, 3H), 6.17 (s, 1H), 6.71 (d, J=8.00 Hz, 1H), 7.34 (d, J=7.60 Hz, 1H), 7.52 (dd, J=2.40, 8.80 Hz, 1H), 7.75 (t, J=8.00 Hz, 1H), 7.98 (d, J=8.80 Hz, 1H), 8.23 (s, 1H), 8.34 (s, 1H), 9.07 (s, 1H). LC/MS: ZORBAX SB C18, 4.6×50 mm, 5 μm; Solvent A=10% MeOH: 90% H2O: 0.1% TFA; Solvent B=90% MeOH: 10% H2O: 0.1% TFA; gradient 0-100% B over 2 min (3 min run time); retention time: 1.713 min; LCMS (ES-API), m/z 392.2 (M+H). HPLC: Sunfire C18 (150×4.6 mm), 3.5 micron; Solvent A=5% ACN: 95% H2O: 0.05% TFA pH=2.5; Solvent B=95% ACN: 5% H2O: 0.05% TFA pH=2.5; gradient 0-100% B over 15 min (23 min run time); Flow rate: 1.0 μl/min; Retention time: 7.274 min; Purity: 98.1%.

Workup

  1. customthoroughly purged with N2 for 5 minutes
  2. customthe reaction mass was once again purged with N2 for 5 minutes
  3. customThe pressure tube was sealed
  4. temperatureThe reaction was cooled to rt
  5. washwashed with DCM
  6. concentrationThe filtrate was concentrated
  7. dissolutiondissolved in 10 mL water
  8. extractionextracted with DCM (3×8 mL)
  9. customThe combined organic layers were dried
  10. concentrationconcentrated
  11. custompurified via preparative HPLC
  12. customto afford Example 176
  13. waitgradient 0-100% B over 15 min (23 min run time)

Sources & evidence

ORD record
ord-ea35625f3d8c441ba5b07cafc462c8ae
Source dataset
uspto-grants-2015_03
Patent number
US08987311B2

Reaction notes

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