Diisopropylethylamine → (S)-3-Fluoro-N6-(1-(4-fluorophenyl)ethyl)-N2-(5-isopropoxy-1H-pyrazol-3-yl)-5-nitropyridine-2,6-diamine

HRID 75888Notes

Reaction equation

HRID 75888 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([N+:19]([O-:21])=[O:20])[C:5]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])=[N:6][C:7]=1F.[CH:22]([O:25][C:26]1[NH:30][N:29]=[C:28]([NH2:31])[CH:27]=1)([CH3:24])[CH3:23].CCN(C(C)C)C(C)C>C1COCC1>[F:1][C:2]1[C:7]([NH:31][C:28]2[CH:27]=[C:26]([O:25][CH:22]([CH3:24])[CH3:23])[NH:30][N:29]=2)=[N:6][C:5]([NH:9][C@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH3:11])=[C:4]([N+:19]([O-:21])=[O:20])[CH:3]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 67452698(S)-5,6-difluoro-N-(1-(4-fluorophenyl)ethyl)-3-nitropyridin-2-amineHCID 1784587215-Isopropoxy-1H-pyrazol-3-amine

Product 1

HCID 178458650(S)-3-Fluoro-N6-(1-(4-fluorophenyl)ethyl)-N2-(5-isopropoxy-1H-pyrazol-3-yl)-5-nitropyridine-2,6-diamineYield 40.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
55 °C

Procedure

To a solution of (S)-5,6-difluoro-N-(1-(4-fluorophenyl)ethyl)-3-nitropyridin-2-amine (Method 23; 0.60 g, 2.0 mmol) in THF (10 ml) at room temperature was added 5-isopropoxy-1H-pyrazol-3-amine (0.50 g, 3.0 mmol), and DIEA (0.29 g, 2.2 mmol). The reaction was then heated to 55° C. for 24 hours, cooled to room temperature, and quenched with water. The reaction was then extracted with DCM (2×75 ml), and the combined organic fractions were dried over Na2SO4, filtered, and then concentrated. The resulting oil was purified by column chromatography (DCM-MeOH=100:1) to give the title compound (0.34 g, 40%). 1H NMR (400 MHz, CD3OD) δ 8.00 (d, J=10.9 Hz, 1H), 7.45-7.35 (m, 2H), 7.07-7.03 (m, 2H), 5.88-5.71 (m, 1H), 5.48-5.30 (m, 1H), 4.58-4.29 (m, 1H), 1.68-1.56 (m, 3H), 1.34-1.28 (m, 6H). MS: Calcd.: 418. Found: [M+H]+ 419.

Workup

  1. temperaturecooled to room temperature
  2. customquenched with water
  3. extractionThe reaction was then extracted with DCM (2×75 ml)
  4. dry with materialthe combined organic fractions were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe resulting oil was purified by column chromatography (DCM-MeOH=100:1)

Sources & evidence

ORD record
ord-c11bd168f60c47519240dfe515015883
Source dataset
uspto-grants-2014_09
Patent number
US08835465B2

Reaction notes

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