2-Fluoro-5-methylphenyl isocyanate → 1-[4-(3-Dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-(2-fluoro-5-methyl-phenyl)-urea

HRID 407502Notes

Reaction equation

HRID 407502 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]=[CH:26][C:25]([CH3:28])=[CH:24][C:23]=1[N:29]=[C:30]=[O:31]>C(Cl)Cl>[CH3:20][N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([NH:13][C:30]([NH:29][C:23]2[CH:24]=[C:25]([CH3:28])[CH:26]=[CH:27][C:22]=2[F:21])=[O:31])=[CH:9][C:8]=1[C:14]1[N:15]([CH3:19])[N:16]=[CH:17][CH:18]=1

Participants

4

Reactant 2

HCID 27333772-Fluoro-5-methylphenyl isocyanateHCID 231395434-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine

Product 1

HCID 231394601-[4-(3-Dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-(2-fluoro-5-methyl-phenyl)-ureaYield 78.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(3-dimethylamino-propoxy)-3-(2-methyl-2H-pyrazol-3-yl)-phenylamine (43.9 mg, 0.160 mmol) in CH2Cl2 (2 mL) was added 2-fluoro-5-methylphenyl isocyanate (0.23 ρL, 0.176 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 139 as a colorless solid (53.2 mg, 78%). LCMS m/z (%)=426 (MH+) (100), 1H NMR (400 MHz, DMSO-d6) δ: 8.98 (bs, 1H), 8.42 (bs, 1H), 7.96 (dd, J=7.89, 1.96 Hz, 1H), 7.45 (d, J=1.82 Hz, 1H), 7.44-7.38 (m, 2H), 7.13-7.06 (m, 2H), 6.82-6.75 (m, 1H), 6.24 (d, J=1.85 Hz, 1H), 3.98 (t, J=6.35 Hz, 2H), 3.66 (s, 3H), 2.25 (s, 3H), 2.19 (t, J=7.03 Hz, 2H), 2.07 (s, 6H), 1.77-1.68 (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-16a785e9b5384e14993a9aef8156eb07
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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