2,3,4-Trifluoro-6-nitroaniline

White to yellow solid

Concentrated nitric acid (1.25 mL) was added drop wise into a solution of 2, 3, 4- trifluoroacetanilide (4.34 g), obtained in step 1, in sulfuric acid (14 mL) at ice bath temperature. After stirring for 4 h, crushed ice was added and the precipitated yellow solid was filtered to afford 6-nitro 2, 3, 4-TRIFLUOROANILINE (1.56 g, 35percent). IR CM-1 (Neat): 3483, 3361, 1664, 1600, 1540, 1515. APOS;H NMR: 8 6. 10 (brs, D20 exchangeable, 2H), 7.80 (m, 1H). MS (E. I.) : M/Z : 192 (M+), 175, 119A solution of 1, 2, 3, 4-tetrafluoro-5-nitrobenzene (1) (1.50 g, 7.69 mmol, 1.00 equiv) and NHAn oven-dried sealable vial was charged with 3f (0.243 g, 1.25 mmol) and 2, 3, 4- trifluoro-6-nitroaniline 4c (0.200 g, 1.04 mmol), evacuated and backfilled with N2 (3 x), and charged with dry DMSO (2 mL), Et3N (0.18 mL, 1.25 mmol) and h (0.132 g, 0.520 mmol). The vial was sealed and the reaction mixture was heated to 60 C for 30 h before cooling to room temperature, diluted with water (20 mL) and extracted with EtOAc (3 x 10 mL). The combined organic layers were washed with brine (2 x 5 mL), dried (Na2S04), filtered, concentrated under reduced pressure, and purified by chromatography on Si02 (EtO Ac/hexanes, 1:4, containing Et3N (0.2%)) to afford 5k (0.221 g, 58 %) as a yellow solid: Mp 157.6-158.4 C; IR (ATR) 3314, 1548, 1474, 1412, 1339, 1256, 1136 cm 1; NMR (400 MHz, acetone-de) d 8.78 (s, 1 H), 8.07 (d, 1 H, 7 = 9.2 Hz), 7.61 (d, 1 H, 7 = 9.2 Hz), 6.76 (brs, 2 H), 6.40 (brs, 1 H), 5.02 (s, 2 H); 13C NMR (100 MHz, acetone-de) d 157.2 (d, 7 = 259.6 Hz), 151.4 (d, 7 = 15.0 Hz), 143.6 (dd, 7 = 231.8, 8.8 Hz), (0276) 142.6-142.2 (m), 139.2 (dd, 7 = 230.7, 7.0 Hz), 135.9 (d, 7 = 14.6 Hz), 133.4 (dd, 7 = 15.6, 10.7 Hz), 127.4 (qd, 7 = 33.6, 3.6 Hz), 123.9 (q, 7 = 271.9 Hz), 121.8-121.4 (m), 121.4 (dq, 7 = 22.0, 3.6 Hz), 107.4 (dd, 7 = 24.9, 2.1 Hz), 44.5-44.3 (m); 19F NMR (376 MHz, acetone-de) d -62.1 (s, 3 F), - 125.1 (s, 1 F), -143.3 (d, 1 F, 7 = 6.6 Hz), -155.7 (d, 1 F, 7 = 6.6 Hz); HRMS (HESI) m/z calcd for Ci H9N402F6 [M+H]+ 367.0624, found 367.0623.A vial containing 2-fluoro-4-(trifluoromethyl)benzylamine 3d (0.20 g, 1.00 mmol) and 2, 3, 4-trifluoro-6- nitroaniline 4c (0.19 g, 1.00 mmol) was evacuated and backfilled with N2 (3 x). Dry DMSO (2.0 mL) was added, followed by Et3N (0.15 mL, 1.06 mmol) and I2 (10 mg, 0.04 mmol). The vial was sealed and the reaction mixture was heated to 120 C for 30 h, cooled to room temperature, diluted with water (20 mL) and extracted with CH2CI2 (3 x 10 mL). The combined organic layers were washed with brine (2 x 10 mL), dried (Na2S04), filtered and concentrated in vacuo. The residue was purified by chromatography on S1O2 (EtO Ac/hexanes, 1:4, containing Et3N (0.2%)) to afford a yellow solid that was recrystallized from CfbCk/hexanes to afford 5f (0.26 g, 71 %) as a bright yellow solid: Mp 108-110 C; IR (ATR) 3500, 3379, 3088, 1644, 1528, 1509, 1431, 1328, 1256, 1126, 909 cm 1; NMR (400 MHz, acetone-d6) d 8.17 (t, 1 H, 7 = 8.0 Hz), 8.07-7.95 (m, 3 H), 7.21 (brs, 2 H), 6.93 (brs, 1 H), 5.32 (d, 2 H, 7 = 6.8 Hz); 13C NMR (100 MHz, acetone-de) d 160.8 (d, 7 = 247.5 Hz), 143.4 (dd, 7 = 233.0, 9.0 Hz), 139.0 (dd, 7 = 230.0, 7.0 Hz), 136.0 (d, 7 = 14.0 Hz), 133.0 (dd, 7 = 16.00, 10.0 Hz), 132.8 (d, 7 = 13.0 Hz), 131.4 (qd, 7 = 33.0, 8.0 Hz), 130.6 (d, 7 = 5.0 Hz), 124.5 (qd, 7 = 270.0, 3.0 Hz), 122.2 (app quint, 7 = 4 Hz), 121.6 (dd, 7 = 10.0, 5.0 Hz), 113.4 (dq, 7 = 25.0, 4.0 Hz), 107.5 (dd, 7 = 25.0, 2.0 Hz), 42.6 (d, 7 = 4.0 Hz); 19F NMR (376 MHz, acetone-de) d -63.1 (s, 3 F), -118.0 (s, 1 F), -144.7 (d, 1 F, 7 = 3.8 Hz), -155.5 (d, 1 F, 7 = 7.5 Hz); HRMS (HESI) m/z calcd for C14H10N3O2F6 [M+H]+ 366.0672, found 366.0669.Synthesis of [3-(dimethylamino)propoxy]-2, 4-difluoro-6-nitroaniline Into a 50-mL 3- necked round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of

Molecular Weight:192.10
XLogP3:1.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:6
Exact Mass:192.01466183
Monoisotopic Mass:192.01466183
Topological Polar Surface Area:71.8
Heavy Atom Count:13
Complexity:211
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes