Isocyanate → HCID 86713639, compound

HRID 1430486Notes

Reaction equation

HRID 1430486 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N:8]=[C:9]=[O:10])[CH:5]=[CH:6][CH:7]=1.[NH2:11][C:12]1[C:13]([F:43])=[CH:14][C:15]([F:42])=[C:16]([C:18]2[C:19](=[O:41])[N:20]([CH2:39][CH3:40])[C:21]3[C:26]([CH:27]=2)=[CH:25][N:24]=[C:23]([N:28]([CH2:30][C:31]2[CH:36]=[CH:35][C:34]([O:37][CH3:38])=[CH:33][CH:32]=2)[CH3:29])[CH:22]=3)[CH:17]=1.[N-]=C=O>C1COCC1.CCOC(C)=O>[CH3:38][O:37][C:34]1[CH:33]=[CH:32][C:31]([CH2:30][N:28]([CH3:29])[C:23]2[CH:22]=[C:21]3[C:26]([CH:27]=[C:18]([C:16]4[C:15]([F:42])=[CH:14][C:13]([F:43])=[C:12]([NH:11][C:9]([NH:8][C:4]5[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=5)=[O:10])[CH:17]=4)[C:19](=[O:41])[N:20]3[CH2:39][CH3:40])=[CH:25][N:24]=2)=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 105034IsocyanateHCID 1230643-Fluorophenyl isocyanateHCID 89611458HCID 89611458, compound

Product 1

HCID 86713639HCID 86713639, compoundYield 79.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

3-Fluorophenyl isocyanate (81 mg, 0.444 mmol) was added to a solution of Example A7 (200 mg, 0.444 mmol) in THF (5 mL) and the mixture was stirred at RT overnight. The reaction was treated with additional isocyanate (10 mg) and stirred at RT for a further 4 h. The mixture was diluted with EtOAc, washed successively with water, satd. NaHCO3, and brine, dried (Na2SO4), concentrated in vacuo, purified by reverse phase chromatography (MeCN/water with 0.1% TFA) and partially concentrated to give an aqueous solution. The solution was diluted with satd. NaHCO3, extracted with EtOAc (2×) and the combined organics were washed with brine, dried (Na2SO4) and evaporated at reduced pressure to give 1-(5-(7-((4-methoxybenzyl)(methyl)amino)-1-ethyl-2-oxo-1,2-dihydro-1,6-naphthyridin-3-yl)-2,4-difluorophenyl)-3-(3-fluorophenyl)urea (207 mg, 79% yield, ˜75% pure) as a light yellow solid, which was used without further purification. MS (ES-API) m/z: 588.2 [M+H]+.

Workup

  1. stirringstirred at RT for a further 4 h
  2. washwashed successively with water
  3. dry with materialNaHCO3, and brine, dried (Na2SO4)
  4. concentrationconcentrated in vacuo
  5. custompurified by reverse phase chromatography (MeCN/water with 0.1% TFA)
  6. concentrationpartially concentrated
  7. customto give an aqueous solution
  8. additionThe solution was diluted with satd
  9. extractionNaHCO3, extracted with EtOAc (2×)
  10. washthe combined organics were washed with brine
  11. dry with materialdried (Na2SO4)
  12. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-e9ccb2458f4f41faa793e92941433205
Source dataset
uspto-grants-2015_01
Patent number
US08940756B2

Reaction notes

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