4-Hexyloxyaniline → HCID 22060317, compound

HRID 76679Notes

Reaction equation

HRID 76679 reaction equation
Cl[C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:14]=[CH:13][C:12]3[O:15][CH2:16][CH2:17][O:18][C:11]=3[CH:10]=2)[C:5]([F:19])=[CH:4][N:3]=1.C(N(CC)C(C)C)(C)C.[CH2:29]([O:35][C:36]1[CH:42]=[CH:41][C:39]([NH2:40])=[CH:38][CH:37]=1)[CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]>C(O)CO>[CH2:17]1[CH2:16][O:15][C:12]2[CH:13]=[CH:14][C:9]([NH:8][C:6]3[C:5]([F:19])=[CH:4][N:3]=[C:2]([NH:40][C:39]4[CH:38]=[CH:37][C:36]([O:35][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34])=[CH:42][CH:41]=4)[N:7]=3)=[CH:10][C:11]=2[O:18]1

Participants

5

Reactant 3

HCID 383604-HexyloxyanilineHCID 81531DiisopropylethylamineHCID 220603622-chloro-5-fluoro-N-(3,4-ethylenedioxyphenyl)-4-pyrimidineamine

Product 1

HCID 22060317HCID 22060317, compoundYield 23.1%

Reagents, catalysts & solvents 1

HCID 174Ethylene GlycolSolvent

Conditions

Temperature
170 °C

Procedure

To a magnetically stirred solution of 2-chloro-N4-(3,4-ethylenedioxyphenyl)-5-fluoro-4-pyrimidineamine (0.25 g, 0.89 mmol) in ethylene glycol (3.0 mL) under nitrogen at room temperature was added N,N-diisopropylethylamine (0.12 g, 0.89 mmol) followed by 4-hexyloxyaniline (0.27 g, 1.4 mmol). The reaction mixture was heated to 170° C. for 5.5 h, cooled to room temperature and partitioned between water (20 mL) and chloroform (20 mL). The aqueous layer was extracted with chloroform (20 mL) and the combined organic layers were dried (Na2SO4), filtered and concentrated in vacuo. The crude brown solid was purified by chromatography (silica gel, 2:1 hexanes/ethyl acetate) to afford N4-(3,4-ethylenedioxyphenyl)-5-fluoro-N2-(4-n-hexyloxyphenyl)-2,4-pyrimidindiamine (0.09 g, 23%) as a white solid: Rf 0.53 (silica gel, 4:1 chloroform/ethyl acetate); mp 115-117° C.; 1H NMR (500 MHz, CDCl3) δ 7.90 (d, J=3.2 Hz, 1H), 7.40 (d, J=8.9 Hz, 2H), 7.29 (d, J=2.5 Hz, 2H), 6.98 (d, J=8.8 Hz, 1H), 6.88-6.82 (m, 3H), 6.61 (s, 1H), 4.29 (d, J=3.1 Hz, 4H), 3.94 (t, J=6.6, 6.7 Hz, 2H), 1.77 (m, 2H), 1.47 (m, 2H), 1.35 (m, 4H), 0.92 (m, 3H); 13C NMR (75 MHz, CDCl3) δ 156.3, 155.1, 150.3, 143.6, 142.7, 140.3, 140.07 139.4, 133.0, 131.7, 121.9, 117.3, 115.0, 114.7, 110.8, 68.6, 64.6, 31.8, 29.5, 25.9, 22.8, 14.2; IR (ATR) 3357 cm−1; ESI MS m/z 439 [C24H27FN4O3+H]+; HPLC (Method B) 98.5% (AUC), tR=7.9 min. Anal. Calcd for C24H27FN4O3: C, 65.74; H, 6.21; N, 12.78. Found: C, 65.34; H, 6.19; N, 12.96.

Workup

  1. temperaturecooled to room temperature
  2. custompartitioned between water (20 mL) and chloroform (20 mL)
  3. extractionThe aqueous layer was extracted with chloroform (20 mL)
  4. dry with materialthe combined organic layers were dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe crude brown solid was purified by chromatography (silica gel, 2:1 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-aa49007cc9b1418cba318c89dab4d3fc
Source dataset
uspto-grants-2014_09
Patent number
US08835430B2

Reaction notes

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