Diisopropylethylamine → HCID 68530418, compound

HRID 2180166Notes

Reaction equation

HRID 2180166 reaction equation
[I:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2(NC)[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[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[CH2:29][N:30](C(C)C)C(C)C>C(Cl)Cl.CCOC(C)=O>[F:17][C:18]1[CH:23]=[C:22]([F:24])[CH:21]=[CH:20][C:19]=1[NH:25][C:26]([NH:30][CH2:29][C:8]1([C:5]2[CH:4]=[CH:3][C:2]([I:1])=[CH:7][CH:6]=2)[CH2:9][CH2:10][N:11]([CH3:14])[CH2:12][CH2:13]1)=[O:27]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5932582,4-Difluorophenyl isocyanateHCID 22490338HCID 22490338, compound

Product 1

HCID 68530418HCID 68530418, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of [4-(4-iodo-phenyl)-1-methyl-piperidin-4-yl]-methylamine (0.20 g, 0.606 mmol) in CH2Cl2 (2 mL) under Ar was added 2,4-difluorophenylisocyanate (0.08 mL, 0.667 mmol, 1.1 eq.) and DIEA (0.106 mL, 0.606 mmol, 1 eq.). The mixture was stirred at room temperature for 16 h then diluted with EtOAc (25 mL) and washed with H2O (20 mL) and saturated brine (20 mL). The organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give a yellow oil which was purified by flash column chromatography by eluting with 3% MeOH/CH2Cl2 (1% TEA) to furnish 1-(2,4-difluoro-phenyl)-3-[4-(4-iodo-phenyl)-1-methyl-piperidin-4-yl-methyl]-urea as a white solid (0.211 g, 0.435 mmol, 72%). 1H NMR (300 MHz, CDCl3): δ 7.84 (br.d, NH), 7.68 (d, 2H), 7.36 (s, 1H), 7.11 (d, 2H), 6.87 (d, 2H), 5.32 (br.s., NH), 3.40 (s, 2H), 2.66 (m, 4H), 2.28 (s, 3H), 2.10 (m, 2H), 1.96 (m, 2H), 1.14 (t, 3H). MS (ESI): 486.1,487.0 (M+1).

Workup

  1. washwashed with H2O (20 mL) and saturated brine (20 mL)
  2. dry with materialThe organic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto give a yellow oil which
  6. customwas purified by flash column chromatography
  7. washby eluting with 3% MeOH/CH2Cl2 (1% TEA)

Sources & evidence

ORD record
ord-86b597868f524651b1b98726c561dafd
Source dataset
uspto-grants-2005_05
Patent number
US06887889B2

Reaction notes

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