Potassium Phosphate, Tribasic → HCID 46944746, compound

HRID 2047232Notes

Reaction equation

HRID 2047232 reaction equation
[C:1]([O:8]C)(=[O:7])[CH2:2][CH2:3][CH2:4][CH:5]=[CH2:6].B1C2CCCC1CCC2.P([O-])([O-])([O-])=O.[K+].[K+].[K+].Cl[C:28]1[CH:33]=[C:32]([N:34](COCC[Si](C)(C)C)COCC[Si](C)(C)C)[N:31]2[N:51]=[CH:52][C:53]([C:54]3[CH:55]=[N:56][C:57]4[C:62]([CH:63]=3)=[CH:61][CH:60]=[CH:59][CH:58]=4)=[C:30]2[N:29]=1>C1COCC1.CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl>[NH2:34][C:32]1[N:31]2[N:51]=[CH:52][C:53]([C:54]3[CH:55]=[N:56][C:57]4[C:62]([CH:63]=3)=[CH:61][CH:60]=[CH:59][CH:58]=4)=[C:30]2[N:29]=[C:28]([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][C:1]([OH:8])=[O:7])[CH:33]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 789669-Borabicyclo(3.3.1)nonaneHCID 520082Methyl 5-HexenoateHCID 86664780(5-Chloro-3-quinolin-3-yl-pyrazolo[1,5-a]pyrimidin-7-yl)-bis-(2-trimethylsilanyl-ethoxymethyl)-amine

Product 1

HCID 46944746HCID 46944746, compoundYield 24.3%

Reagents, catalysts & solvents 3

HCID 178418807HCID 178418807, compoundCatalystHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl hex-5-enoate (12 mg, 0.1 mmol) in THF (0.5 ml) under argon at 0° C. was added 9-BBN (0.2 mmol, 0.4 ml of 0.5 M solution in THF). The mixture was warmed to room temperature and stirred for 16 h. Potassium phosphate (3 M in H2O, 0.2 mmol) was added followed by the addition of 5-chloro-3-(quinolin-3-yl)-N,N-bis((2-(trimethylsilyl)ethoxy)methyl)pyrazolo[1,5-a]pyrimidin-7-amine (50 mg, 0.09 mmol) in DMF (0.5 ml) and Pd(dppf)Cl2—CH2Cl2 (5 mg, 0.005 mmol). The reaction mixture was heated at 90° C. for 16 h under argon. The solution was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in 2:1 THF: MeOH (3 mL) and was treated with 2N NaOH(aq) (0.25 mL). The resulting solution was stirred at room temperature for 4 hours followed by the addition of 2N hydrochloride solution (1.0 ml). The solution was heated at 65° C. for 2 h, cooled to room temperature, concentrated in vacuo and purified by prep-LC to afford the title compound (8.2 mg): LC/MS RT=2.74 min. Mass calculated for, M+H 376.17, observed 376.17.

Workup

  1. temperatureThe reaction mixture was heated at 90° C. for 16 h under argon
  2. temperatureThe solution was cooled to room temperature
  3. concentrationconcentrated under reduced pressure
  4. dissolutionThe residue was dissolved in 2:1 THF
  5. additionMeOH (3 mL) and was treated with 2N NaOH(aq) (0.25 mL)
  6. stirringThe resulting solution was stirred at room temperature for 4 hours
  7. additionfollowed by the addition of 2N hydrochloride solution (1.0 ml)
  8. temperatureThe solution was heated at 65° C. for 2 h
  9. temperaturecooled to room temperature
  10. concentrationconcentrated in vacuo
  11. custompurified by prep-LC

Sources & evidence

ORD record
ord-6e625ae989ea43e1a1d00ef891969fd5
Source dataset
uspto-grants-2013_11
Patent number
US08591943B2

Reaction notes

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