Triphenylphosphine → HCID 178486931, compound

HRID 407338Notes

Reaction equation

HRID 407338 reaction equation
[F:1][C:2]1[C:3](OC)=[CH:4][C:5]2[S:9][C:8]([CH2:10][C:11]#[N:12])=[N:7][C:6]=2[CH:13]=1.[CH:16]1([C:19](Cl)=O)[CH2:18][CH2:17]1.[C:22]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[OH2:41].[NH2:42][NH2:43]>ClCCl.CN(C1C=CN=CC=1)C.Cl.C(O)C.C(N(CC)CC)C.C(Cl)(Cl)(Cl)Cl>[CH:16]1([C:19]2[C:10]([C:8]3[S:9][C:5]4[CH:4]=[C:3]([O:41][CH3:22])[C:2]([F:1])=[CH:13][C:6]=4[N:7]=3)=[C:11]([NH2:12])[NH:42][N:43]=2)[CH2:18][CH2:17]1

Participants

11

Reactant 4

HCID 11776TriphenylphosphineHCID 24654Hydrazine hydrate (1:1)HCID 77637Cyclopropanecarbonyl chlorideHCID 45076994HCID 45076994, compound

Product 1

HCID 178486931HCID 178486931, compoundYield 29%

Reagents, catalysts & solvents 6

HCID 313Hydrochloric AcidCatalystHCID 142844-(Dimethylamino)pyridineCatalystHCID 702EthanolSolventHCID 5943Carbon TetrachlorideSolventHCID 6344DichloromethaneSolventHCID 8471TriethylamineSolvent2×

Procedure

To a 10 mL reaction vessel containing (5-fluoro-6-methoxybenzothiazol-2-yl) acetonitrile (100 mg, 0.45 mmol) in 4 mL of anhydrous dichloromethane were added cyclopropane carbonyl chloride (21 μL, 0.231 mmol), 1.35 equivalents of triethylamine (85 μL) and a catalytic amount of DMAP (10 mg). The reaction was agitated at room temperature for approximately 3 hrs. At this point the solvent was evaporated and CCl4 (4 mL), 2.5 equivalents of polystyrene resin bound triphenylphosphine (725 mg, 1.55 mmol/g), and triethylamine (85 μL) were added. After agitation at 65° C. for a minimum of 3 hrs, the reaction mixture was concentrated. Ethanol (4 mL) and hydrazine monohydrate (40 μL, 1.8 equivalents) were then added and the mixture was refluxed for approximately 6 hrs. Several drops of concentrated HCl were then added to ensure complete cyclization of the pyrazole ring. After completion of the reaction, the solids were removed by filtration and the resin was washed three times with 10% methanol in dichloromethane. The filtrate was then concentrated and purified by flash column chromatography eluting with CH2Cl2:MeOH=50:1 to yield 40 mg (29%) of the title compound as a cream coloured solid. MS (m/z, ES+): 305.1 (M+1, 100%)

Workup

  1. customTo a 10 mL reaction vessel
  2. customAt this point the solvent was evaporated
  3. additionwere added
  4. concentrationAfter agitation at 65° C. for a minimum of 3 hrs, the reaction mixture was concentrated
  5. temperaturethe mixture was refluxed for approximately 6 hrs
  6. customAfter completion of the reaction
  7. customthe solids were removed by filtration
  8. washthe resin was washed three times with 10% methanol in dichloromethane
  9. concentrationThe filtrate was then concentrated
  10. custompurified by flash column chromatography
  11. washeluting with CH2Cl2

Sources & evidence

ORD record
ord-1bb0b99760294860b8062c738a2c9c7e
Source dataset
uspto-grants-2014_06
Patent number
US08754233B2

Reaction notes

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