Phenyl isocyanate → HCID 71585075, compound

HRID 1257224Notes

Reaction equation

HRID 1257224 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-0a28060400f340d7bfbdb348a3771e65
Source dataset
uspto-grants-2013_06
Patent number
US08461179B1

Reaction notes

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