Triphenylphosphine → 1-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3-(2,4-difluorophenyl)urea

HRID 1362938Notes

Reaction equation

HRID 1362938 reaction equation
[Cl:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[O:17])[CH:11]=[CH:12][C:13]=1[OH:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:47][CH2:48][N:49]1[CH2:53][CH2:52][CH2:51][CH2:50]1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[Cl:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=2[F:26])=[O:17])[CH:11]=[CH:12][C:13]=1[O:14][CH2:47][CH2:48][N:49]1[CH2:53][CH2:52][CH2:51][CH2:50]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 762881-PyrrolidineethanolHCID 1356979371-[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-urea

Product 1

HCID 454867381-(3-(4-chloro-1-methyl-1H-pyrazol-5-yl)-4-(2-(pyrrolidin-1-yl)ethoxy)phenyl)-3-(2,4-difluorophenyl)ureaYield 52.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-[3-(4-chloro-2-methyl-2H-pyrazol-3-yl)-4-hydroxy-phenyl]-3-(2,4-difluoro-phenyl)-urea (0.35 g, 0.09 mmol) in anhydrous THF (2 mL), triphenyl phosphine (70.8 mg, 0.27 mmol) and 1-(2-hydroxyethyl)-pyrrolidine (0.032 mL, 0.27 mmol) were added followed by dropwise addition of diisopropyl azodicarboxylate (DIAD) (0.052 mL, 0.27 mmol). The reaction mixture was stirred at room temperature for 2 hours, concentrated to give a crude product that was subjected to purification by preparative HPLC. The proper fractions were collected, neutralized with 1N NaOH and extracted with EtOAc four times. The solution was evaporated under reduced pressure to afford Compound 13 as an off-white solid in 52.8% yield. LCMS m/z (%)=476 (M+H 35Cl, 100), 478 (M+H 37Cl, 40). 1H NMR (400 MHz, DMSO-d6) δ: 9.10 (s, 1H), 8.55 (s, 1H), 8.17-8.09 (m, 1H), 7.69 (s, 1H), 7.61 (dd, J=8.97 and 2.72 Hz, 1H), 7.47 (d, J=2.70 Hz, 1H), 743-7.36 (m, 1H), 7.26 (d, J=9.04 Hz, 1H), 7.16-7.09 (m, 1H), 4.25-4.08 (m, 2H), 3.73 (s, 3H), 2.58-2.45 (m, 2H), 2.45-2.29 (m, 4H), 1.75-1.69 (m, 4H).

Workup

  1. concentrationconcentrated
  2. customto give a crude product that
  3. customwas subjected to purification by preparative HPLC
  4. customThe proper fractions were collected
  5. extractionextracted with EtOAc four times
  6. customThe solution was evaporated under reduced pressure

Sources & evidence

ORD record
ord-48099efdb65944859e7e3b6c7a80646d
Source dataset
uspto-grants-2011_02
Patent number
US07884101B2

Reaction notes

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