Yield:175204-19-0 62.6%

Reaction Conditions:

with pyridine;4-pyrrolidin-1-ylpyridine in acetonitrile; for 72 h;Inert atmosphere;Reflux;

Steps:

2 Example 2: Synthesis of methyl 3,4-diamino-/V, /V-b/^'s-(toluene-4- sulfonylamino)benzoate (12)

Methyl 3, 4-diaminobenzoate (10) (1.0 g, 0.006 mol), p-toluenesulfonyl chloride (11 ) (2.52 g, 0.013 mol) and 4-pyrrolidinopyridine (0.90 g, 0.006 mol) were added to dry acetonitrile (25 mL) under argon. Dry pyridine (2.4 mL, 0.03 mol) was then added and the resulting solution was heated at reflux for 72 hours. After this time, the acetonitrile was removed invacuo to afford a brown oily residue. The residue was dissolved in dichloromethane (DCM) (30 mL) and washed with 0.5 M HCI (3 ^χ 30 mL). The organic layer was dried (MgS0₄) and the solvent removed invacuo to yield a brown powder, which was purified by column chromatography on silica, eluting with DCM : methanol (95 : 5) to afford crudemethyl 3,4-diamino-6/^'s-(toluene-4-sulfonylamino)benzoate(12). This was recrystallised from DCM : petroleum ether to yield pure methyl 3,4-diamino-/5/^'s- (toluene-4-sulfonylamino)benzoate (12) as brown crystals (1.78 g, 62.6 %); mp 175 °C; R_f = 0.44 (DCM : methanol, 9 : 1); m/z 496.9 (MNa⁺); Analysis Calcd. for C22H22N2O₆S2: C, 55.68; H, 4.67; N, 5.90 %. Found C, 55.86; H, 4.70; N, 5.74 %; v_max (KBr) / cm^"1 3217 (NH), 1704 (C=0), 1157 (S=0); δ_Η (d₆-DMSO, 300 MHz) 9.62 (2H, s, 2 NH), 7.67 (2H, d, J= 8.4,H₂J H₆. orH₂- /H₆-), 7.62 (1 H, dd, J_6, 5 = 8.4, J_6, 2 = 1.8, H₆), 7.57 (3H, m, H₂ and Η₂· / Η₆. ΟΓ H₂- / H₆-),7.36 (4H, d, J= 8.4, H₃'/ H₅. andH₃"/ H₅ ^{FontWeight="Bold" FontSize="10"} ) 7.26 (1 H, d, J₅, e = 8.4, H₅), 3.74 (3H, s, OCH₃), 2.36 (3H, s, CH₃), 2.35 (3H, s, CH₃);5_C (d₆-DMSO, 75 MHz)165.5 (CO), 144.5 (C₄ and C₄"), 144.3 (C₄), 136.4 (C_r and C ), 135.8 (C₃), 130.3 (C₃J C₅. or C₃ ^{FontWeight="Bold" FontSize="10"} / C₅ ), 130.3 (C₃J C₅' or C₃"/ C₅"), 127.7 (C₆), 127.4 (C₂J C₆. or C₂ ^{FontWeight="Bold" FontSize="10"} / C_e ^{FontWeight="Bold" FontSize="10"} ), 127.4 (C₂J C_e- or C₂- / C₆"), 125.7 (C₂), 125.6 (d), 120.5 (C₅), 52.6 (OCH₃), 21.5 (2 CH₃).

References:

WO2014/96864,2014,A1 Location in patent:Paragraph 00177