3-Fluorophenyl isocyanate → HCID 89606284, compound

HRID 1430456Notes

Reaction equation

HRID 1430456 reaction equation
[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([CH3:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH2:19][CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([Cl:18])[CH:12]=3)[CH:7]=1.[F:24][C:25]1[CH:26]=[C:27]([N:31]=[C:32]=[O:33])[CH:28]=[CH:29][CH:30]=1>C1COCC1>[Cl:18][C:13]1[CH:12]=[C:11]2[C:16]([CH:17]=[C:8]([C:6]3[C:5]([CH3:22])=[CH:4][C:3]([F:23])=[C:2]([NH:1][C:32]([NH:31][C:27]4[CH:28]=[CH:29][CH:30]=[C:25]([F:24])[CH:26]=4)=[O:33])[CH:7]=3)[C:9](=[O:21])[N:10]2[CH2:19][CH3:20])=[CH:15][N:14]=1

Participants

4

Reactant 2

HCID 1230643-Fluorophenyl isocyanateHCID 87666922HCID 87666922, compound

Product 1

HCID 89606284HCID 89606284, compoundYield 31.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Example A6 (0.200 g, 0.603 mmol) and TEA (0.126 mL, 0.904 mmol) in THF (6 mL) was treated with 3-fluorophenyl isocyanate (0.083 ml, 0.723 mmol) and stirred at RT for 4 h. The mixture was concentrated to dryness and purified via silica gel chromatography (EtOAc/Hex). The material was treated with DCM and the solid collected via filtration. The filtrate was concentrated to dryness, re-purified via silica gel chromatography (MeOH/DCM) and combined with the isolated solid to afford 1-(5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluoro-4-methylphenyl)-3-(3-fluorophenyl)urea (88 mg, 31% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.23 (s, 1H), 8.77 (s, 1H), 8.58 (d, J=2.3 Hz, 1H), 8.00 (s, 1H), 7.97 (d, J=8.4 Hz, 1H), 7.73 (s, 1H), 7.46 (dt, J=12.0, 2.3 Hz, 1H), 7.28 (m, 1H), 7.18 (d, J=12.2 Hz, 1H), 7.05 (ddd, J=8.2, 2.0, 0.9 Hz, 1H), 6.77 (td, J=8.3, 2.5 Hz, 1H), 4.27 (q, J=7.1 Hz, 2H), 2.07 (s, 3H), 1.21 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 469.1 [M+H]+.

Workup

  1. concentrationThe mixture was concentrated to dryness
  2. custompurified via silica gel chromatography (EtOAc/Hex)
  3. additionThe material was treated with DCM
  4. filtrationthe solid collected via filtration
  5. concentrationThe filtrate was concentrated to dryness
  6. customre-purified via silica gel chromatography (MeOH/DCM)

Sources & evidence

ORD record
ord-7af2d5e30db1401b8eae03e63e655c76
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

Loading…