2,4-Difluorophenyl isocyanate → HCID 11497283, compound

HRID 1362990Notes

Reaction equation

HRID 1362990 reaction equation
[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH2:22])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][N:17]1[CH2:21][CH2:20][CH2:19][CH2:18]1.[F:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:25]=1[N:31]=[C:32]=[O:33]>CC(N(C)C)=O.CS(C)=O>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:22][C:32]([NH:31][C:25]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:24]=2[F:23])=[O:33])[CH:11]=[CH:12][C:13]=1[O:14][CH2:15][CH2:16][N:17]1[CH2:18][CH2:19][CH2:20][CH2:21]1

Participants

5

Reactant 2

HCID 5932582,4-Difluorophenyl isocyanateHCID 58964277HCID 58964277, compound

Product 1

HCID 11497283HCID 11497283, compoundYield 59%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyrrolidin-1-yl-ethoxy)-phenylamine (0.96 g, 2.47 mmol) in 10 mL of DMA was added 2,4-difluoro phenyl isocyanate (0.42 g, 2.71 mmol), and the mixture was stirred at ambient temperature overnight The reaction mixture was diluted with DMSO and was purified by RP-HPLC. The fractions containing the product were pooled and evaporated to a small volume. The aqueous solution was neutralized with 1N NaOH to a pH of 9.0 and the product was extracted with ethyl acetate (2×, 50 mL). The organic layer was dried with sodium sulfate, filtered and evaporated to dryness to produce 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-3-(2,4-difluoro-phenyl)-urea as a colorless solid in 59% yield. LCMS m/z (%)=520 (M+H 79Br, 100), 522 (M+H 81Br, 98). 1H NMR (400 MHz. DMSO-d6) δ: 9.03 (bs, 1H), 8.49 (bs, 1H), 8.01-8.1 (m, 1H), 7.61 (s, 1H), 7.51 (dd, J=8.96 and 2.73 Hz, 1H), 7.35 (d, J=2.72 Hz, 1H), 7.27-7.33 (m, 1H), 7.15 (d, J=9.04 Hz, 1H), 7.04-7.09 (m, 1H), 4.01-4.11 (m, 2H), 3.67 (s, 3H), 2.51-2.73 (m, 2H), 2.34-2.38 (bs, 4H), 1.59-1.63 (bs, 4H).

Workup

  1. customwas purified by RP-HPLC
  2. additionThe fractions containing the product
  3. customevaporated to a small volume
  4. extractionthe product was extracted with ethyl acetate (2×, 50 mL)
  5. dry with materialThe organic layer was dried with sodium sulfate
  6. filtrationfiltered
  7. customevaporated to dryness

Sources & evidence

ORD record
ord-1b847b799b3f4a889ef0b85206471654
Source dataset
uspto-grants-2011_02
Patent number
US07884101B2

Reaction notes

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