2,4-Difluorophenyl isocyanate → 1-(2,4-Difluoro-phenyl)3-[4-(3-dimethylamino-propoxy)3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-urea

HRID 407499Notes

Reaction equation

HRID 407499 reaction equation
[CH3:1][N:2]([CH3:20])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH2:13])=[CH:9][C:8]=1[C:14]1[N:15]([CH3:19])[N:16]=[CH:17][CH:18]=1.[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[N:29]=[C:30]=[O:31]>C(Cl)Cl>[F:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:23]=1[NH:29][C:30]([NH:13][C:10]1[CH:11]=[CH:12][C:7]([O:6][CH2:5][CH2:4][CH2:3][N:2]([CH3:1])[CH3:20])=[C:8]([C:14]2[N:15]([CH3:19])[N:16]=[CH:17][CH:18]=2)[CH:9]=1)=[O:31]

Participants

4

Reactant 2

HCID 5932582,4-Difluorophenyl isocyanateHCID 231395434-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine

Product 1

HCID 231395521-(2,4-Difluoro-phenyl)3-[4-(3-dimethylamino-propoxy)3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-ureaYield 90.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine (21.4 mg, 0.078 mmol) in CH2Cl2 (2 mL) was added 2,4-difluorophenyl isocyanate (0.10 μL, 0.084 mmol) and stirred for two hours. The resulting material was purified by solid phase extraction (SCX, 1 gram cartridge), eluting with methanol (30 mL) followed by 2M NH3 in methanol (30 mL). The NH3 containing fractions were dried in vacuo to afford Compound 124 as a colorless solid (30.2 mg, 73%). LCMS m/z (%)=430 (MH+) (100), 1H NMR (400 MHz, DMSO-d6) δ: 8.94 (bs, 1H), 8.46 (bs, 1H), 8.09-8.00 (m, 1H), 7.45 (d, J=1.80 Hz, 1H), 7.42 (dd, J=8.89, 2.72 Hz, 1H), 7.34-7.26 (m, 1H), 7.09 (d, J=8.94 Hz, 1H), 7.06-6.99 (m, 1H), 6.24 (d, J=1.83 Hz, 1), 3.97 (t, J=6.32 Hz, 2H), 3.65 (s, 3H), 2.23 (t, J=7.07 Hz, 2H), 2.10 (s, 6H), 1.78-1.69 (m, 2H).

Workup

  1. customThe resulting material was purified by solid phase extraction (SCX, 1 gram cartridge)
  2. washeluting with methanol (30 mL)
  3. dry with materialThe NH3 containing fractions were dried in vacuo

Sources & evidence

ORD record
ord-c61fe2532eec487296582cd3e70422f4
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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