Water → HCID 10172395, compound

HRID 1179133Notes

Reaction equation

HRID 1179133 reaction equation
FC(F)(F)S(O[C:7]1[CH:8]=[CH:9][C:10]2[N:11]([N:13]=[CH:14][C:15]=2[C:16]2[CH:21]=[CH:20][N:19]=[C:18]([NH:22][CH:23]3[CH2:25][CH2:24]3)[N:17]=2)[N:12]=1)(=O)=O.[C:28]1([SH:34])[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.CC([O-])(C)C.[Na+].O>CS(C)=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:23]1([NH:22][C:18]2[N:17]=[C:16]([C:15]3[CH:14]=[N:13][N:11]4[C:10]=3[CH:9]=[CH:8][C:7]([S:34][C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)=[N:12]4)[CH:21]=[CH:20][N:19]=2)[CH2:24][CH2:25]1

Participants

7

Reactant 4

HCID 962WaterHCID 7969ThiophenolHCID 10172978HCID 10172978, compoundHCID 23676156Sodium t-butoxide

Product 1

HCID 10172395HCID 10172395, compoundYield 36%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 3-[2-(cyclopropylamino)-4-pyrimidinyl]pyrazolo[1,5-b]pyridazin-6-yl trifluoromethanesulfonate (250 mg, 0.625 mmol) in DMSO (8 mL) was added Pd(PPh3)4 (29 mg, 0.025 mmol), benzene thiol (0.064 mL, 0.625 mmol), and NaOtBu (120 mg, 1.31 mmol). The reaction mixture was heated at an oil bath temperature of 100° C. for about 2 hours. The mixture was cooled to RT and water (40 mL) was added. The aqueous layer was washed with EtOAc (3×60 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo and purified by silica-gel column chromatography (gradient 50-100% EtOAc in hexanes) to give the title compound as a yellow solid (80 mg, 36%). 1H-NMR (400 MHz, CDCl3) δ 8.90 (d, 1H, J=9.1 Hz), 8.34 (s, 1H), 8.29 (bs, 1H), 7.67 (m, 2H), 7.47 (m, 3H), 6.92 (d, 1H, J=5.3 Hz), 6.88 (d, 1H, J=9.4 Hz), 5.38 (s, 1H), 2.82 (m, 1H), 0.85 (m, 2H), 0.61 (m, 2H); MS (ESI) (M+H)+ 361.

Workup

  1. temperatureThe mixture was cooled to RT
  2. washThe aqueous layer was washed with EtOAc (3×60 mL)
  3. dry with materialThe combined organic layers were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. custompurified by silica-gel column chromatography (gradient 50-100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-c57f5407a630481fb75d3f8b0e6de507
Source dataset
uspto-grants-2007_10
Patent number
US07279473B2

Reaction notes

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