Phenyl isocyanate → HCID 71585075, compound

HRID 1430512Notes

Reaction equation

HRID 1430512 reaction equation
[NH2:1][C:2]1[C:3]([F:23])=[CH:4][C:5]([Br:22])=[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH3:19])[CH:12]=3)[CH:7]=1.[C:24]1([N:30]=[C:31]=[O:32])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>C(Cl)Cl>[Br:22][C:5]1[C:6]([C:8]2[C:9](=[O:21])[N:10]([CH3:20])[C:11]3[C:16]([CH:17]=2)=[CH:15][N:14]=[C:13]([NH:18][CH3:19])[CH:12]=3)=[CH:7][C:2]([NH:1][C:31]([NH:30][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)=[O:32])=[C:3]([F:23])[CH:4]=1

Participants

4

Reactant 2

HCID 7672Phenyl isocyanateHCID 86713658HCID 86713658, compound

Product 1

HCID 71585075HCID 71585075, compoundYield 44%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 3-(5-amino-2-bromo-4-fluoro-phenyl)-1-methyl-7-methylamino-1H-[1,6]naphthyridin-2-one (420 mg, 1.16 mmol) in DCM (25 mL) was treated with phenyl isocyanate (0.19 g, 1.62 mmol) and TEA (0.326 g, 3.23 mmol) and stirred at RT for 12 h. The mixture was concentrated under reduced pressure and washed with MTBE (1×). The crude product was purified by prep-HPLC separation (MeCN/H2O with 0.1% TFA) to give 1-(4-bromo-2-fluoro-5-(1-methyl-7-(methylamino)-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)phenyl)-3-phenylurea (245 mg, 44% yield). 1H NMR (400 MHz, DMSO-d6): δ 9.08 (s, 1H), 8.67 (s, 1H), 8.40 (s, 1H), 8.17 (d, J=8.8 Hz, 1H), 7.70 (s, 1H), 7.64 (d, J=10.8 Hz, 1H), 7.40 (d, J=7.6 Hz, 2H), 7.28-7.24 (t, J=7.6 Hz, 2H), 7.04-7.03 (m, 1H), 6.98-6.94 (t, J=8 Hz, 1H), 6.17 (s, 1H), 3.50 (s, 3H), 2.85 (d, J=4.8 Hz, 3H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. washwashed with MTBE (1×)
  3. customThe crude product was purified by prep-HPLC separation (MeCN/H2O with 0.1% TFA)

Sources & evidence

ORD record
ord-7c2a537628a64fc28a036191083147f8
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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