1,3-Difluoro-5-isocyanatobenzene → HCID 86713665, compound

HRID 1257233Notes

Reaction equation

HRID 1257233 reaction equation
[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Cl: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:32]=[C:33]=[O:34])[CH:28]=[C:29]([F:31])[CH:30]=1>C1COCC1>[Cl:22][C:5]1[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][C:2]([NH:1][C:33]([NH:32][C:27]2[CH:28]=[C:29]([F:31])[CH:30]=[C:25]([F:24])[CH:26]=2)=[O:34])=[C:3]([F:23])[CH:4]=1

Participants

4

Reactant 2

HCID 27792821,3-Difluoro-5-isocyanatobenzene3×HCID 877715763-(5-Amino-2-chloro-4-fluorophenyl)-7-chloro-1-ethyl-1,6-naphthyridin-2(1h)-one

Product 1

HCID 86713665HCID 86713665, compoundYield 61.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of Example A3 (0.20 g, 0.568 mmol) in THF (6 mL) was treated with TEA (0.098 mL, 0.710 mmol) followed by 3,5-difluorophenyl isocyanate (0.092 g, 0.596 mmol) and stirred at RT for 2 h. Additional 3,5-difluorophenyl isocyanate (0.14 g, 0.903 mmol) was added and the mixture stirred at RT overnight. More 3,5-difluorophenyl isocyanate (0.25 g, 1.61 mmol) was added and the mixture stirred at RT for 24 h. The mixture was cooled to 0° C. and the solids collected via filtration and dried. The filtrate was concentrated to dryness and purified via silica gel chromatography (THF/Hex) and combined with the isolated solid to afford 1-(4-chloro-5-(7-chloro-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2-fluorophenyl)-3-(3,5-difluorophenyl)urea (177 mg, 61% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.27 (br s, 2H), 8.79 (s, 1H), 8.15 (d, J=8.5 Hz, 1H), 8.08 (s, 1H), 7.74 (s, 1H), 7.57 (d, J=10.9 Hz, 1H), 7.16 (m, 2H), 6.77 (m, 1H), 4.27 (q, J=7.0 Hz, 2H), 1.20 (t, J=7.0 Hz, 3H); MS (ESI) m/z: 507.1 [M+H]+.

Workup

  1. stirringthe mixture stirred at RT overnight
  2. stirringthe mixture stirred at RT for 24 h
  3. temperatureThe mixture was cooled to 0° C.
  4. filtrationthe solids collected via filtration
  5. customdried
  6. concentrationThe filtrate was concentrated to dryness
  7. custompurified via silica gel chromatography (THF/Hex)

Sources & evidence

ORD record
ord-7420e7310e9a48a9bb9866a61d9f17ad
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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