2,4-Difluorophenyl isocyanate → Nelotanserin

HRID 540485Notes

Reaction equation

HRID 540485 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]([NH2:16])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15].[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[N:25]=[C:26]=[O:27]>C(Cl)Cl>[Br:1][C:2]1[CH:6]=[N:5][N:4]([CH3:7])[C:3]=1[C:8]1[CH:9]=[C:10]([NH:16][C:26]([NH:25][C:19]2[CH:20]=[CH:21][C:22]([F:24])=[CH:23][C:18]=2[F:17])=[O:27])[CH:11]=[CH:12][C:13]=1[O:14][CH3:15]

Participants

4

Reactant 2

HCID 5932582,4-Difluorophenyl isocyanateHCID 115727413-(4-Bromo-1-methyl-1H-pyrazol-5-yl)-4-methoxyaniline

Product 1

HCID 11683556NelotanserinYield 72.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenylamine (0.027 g, 0.095 mmol) was treated with 2,4-difluorophenyl isocyanate (0.015 g, 11.5 μL, 0.095 mmol, 1.0 equiv.) in CH2Cl2 (2 mL), in a similar manner as described in Example 1.2 to afford Compound 8 (0.030 g, 0.069 mmol, 71%) as a white solid. LCMS m/z (%)=437 (M+H79Br, 100), 439 (M+H81Br, 91). 1H NMR (400 MHz, acetone-d6) δ: 8.45 (s, 1H), 8.23 (dt, J=6.1, 9.2 Hz, 1H), 7.93 (s, 1H), 7.68 (dd, J=2.6, 9.0 Hz, 1H), 7.49 (s, 1H), 7.44 (d, J=2.6 Hz, 1H), 7.14 (d, J=9.0 Hz, 1H), 7.07 (ddd, J=2.7, 8.7, 11.3 Hz, 1H), 6.93-7.02 (m, 1H), 3.82 (s, 3H), 3.69 (s, 3H).

Sources & evidence

ORD record
ord-f331267ab28343baa0221c02191079cc
Source dataset
uspto-grants-2014_10
Patent number
US08871797B2

Reaction notes

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