Reaction SMILES: [NH:1]1[C:5]2[CH:6]=[CH:7][S:8][C:4]=2[C:3]([C:9]2[NH:10][C:11]3[C:16]([CH:17]=2)=[CH:15][CH:14]=[C:13]([C:18]([OH:20])=O)[CH:12]=3)=[N:2]1.C1CCC(N=C=NC2CCCCC2)CC1.C1C=CC2N(O)N=NC=2C=1.[O:46]1[C:50]2[CH:51]=[CH:52][C:53]([CH2:55][N:56]3[CH2:61][CH2:60][NH:59][CH2:58][CH2:57]3)=[CH:54][C:49]=2[O:48][CH2:47]1.C(O)C(N)(CO)CO>C(Cl)Cl>[O:46]1[C:50]2[CH:51]=[CH:52][C:53]([CH2:55][N:56]3[CH2:57][CH2:58][N:59]([C:18]([C:13]4[CH:12]=[C:11]5[C:16]([CH:17]=[C:9]([C:3]6[C:4]7[S:8][CH:7]=[CH:6][C:5]=7[NH:1][N:2]=6)[NH:10]5)=[CH:15][CH:14]=4)=[O:20])[CH2:60][CH2:61]3)=[CH:54][C:49]=2[O:48][CH2:47]1
Reactant: O=C(O)c1ccc2cc(-c3n[nH]c4ccsc34)[nH]c2c1
Reactant: c1cc2c(cc1CN1CCNCC1)OCO2
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: NC(CO)(CO)CO
Agent: On1nnc2ccccc21
Solvent: ClCCl
Product: O=C(c1ccc2cc(-c3n[nH]c4ccsc34)[nH]c2c1)N1CCN(Cc2ccc3c(c2)OCO3)CC1
Reaction time: 0.25 h

Procedure:
A solution of lithium diisopropylamide (1.8M, 50.5 ml, 90.9 mmol, 2.5 eq) was added to a solution of indole-1,6-dicarboxylic acid, 1-tert-butyl ester-6-methyl ester [10 g, 38.4 mmol, Intermediate (34)] in tetrahydrofuran (160 ml) at −78° C. The resulting mixture was stirred for 2 hours at −78° C. before a solution of trimethyltin chloride in tetrahydrofuran (1M, 145.5 ml, 4 eq) was added. The resulting solution was warmed to 0° C. for 15 minutes and partitioned twice between ethyl acetate (150 ml) and aqueous half-saturated ammonium chloride solution (200 ml). The organic layers were combined and dried over magnesium sulfate and concentrated. The residue was purified by flash column chromatography (10% ethyl acetate in heptane) to give trimethyl(indole- 1,6-dicarboxylic acid, 1-tert-butyl ester-6-methyl ester)tin [8.7 g, Intermediate (37)] LC/MS: 440 (M+H); RT=2.5 minutes; 1H NMR [(CD3)2SO)]: δ 8.8 (1H, t), 7.8 (1H, d), 6.8 (1H, t), 3.9 (3H, s), 1.7 (9H, s). Step 2. A solution of trimethyl(indole- 1,6-dicarboxylic acid, 1-tert-butyl ester-6-methyl ester)tin [7.5 g, 17.1 mmol, 2 eq, Intermediate (37)] in dioxane (30 ml) was added in two equal portions over 2 hours to a solution of 3-iodo-thieno[3,2-c]pyrazole-1-carboxylic acid tert-butyl ester [3 g, 8.6 mmol 1 eq, Example 5B above], copper iodide (171 mg, 0.43 mmol, 0.1 eq) and tetrakis(triphenyl-phosphine) palladium (497 mg, 0.43 mmol, 0.05 eq) in dioxane. The mixture was heated to 90° C. and stirred for 24 hours. Then the solution was cooled to room temperature and partitioned three times between ethyl acetate (150 ml) and a 3:1 mixture of aqueous saturated NaHCO3 solution and brine (300 ml). The combined organic layers were washed with brine (250 ml), dried over magnesium sulfate and concentrated. The residue was subjected to flash column chromatography (20% ethyl acetate in heptane) and a solution of the crude product (5.45 g, a mixture of 2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indole-6-carboxylic acid methyl ester, 1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester, 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 6-methyl ester, and 2-(1-tert-butoxycarbonyl-1H-thieno[3,2-c]pyrazol-3-yl)-indole-1,6-dicarboxylic acid 1-tert-butyl ester 6-methyl ester) in a mixture of tetrahydrofuran and water (50 ml, 1:1) was treated with potassium hydroxide (1.1 g, 19 mmol, 2 eq) at 60° C. The reaction mixture was stirred overnight and then cooled to room temperature. To the solution 1N hydrochloric acid was added to make pH around 6. The solid was filtered, washed with water, heptane and dried to afford 2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indole-6-carboxylic acid [3.18 g, Intermediate (38)] which was used without further purification. LC/MS: 282 (M−H, negative mode). Step 3. The mixture of 2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indole-6-carboxylic acid [100 mg, 1.5 eq, Intermediate (38)], PS-DCC (2 eq) and HOBT (1.7 eq) in DCM (5 ml) was shaken for 15 minutes. Then 1-benzo[1,3]dioxol-5-ylmethyl-piperazine was added and the reaction mixture was shaken at room temperature overnight. PS-trisamine (4 eq) was added and the mixture was shaken at room temperature overnight. The resin was filtered, washed with DCM and the filtrate was concentrated. The residue was purified by column chromatography (20% ethyl acetate in heptane) affording (4-benzo[1,3]dioxol-5-ylmethyl-piperazin-1-yl)-[2-(1H-thieno[3,2-c]pyrazol-3-yl)-1H-indol-6-yl]-methanone [Example 45]. LC/MS: 486 (M+H), RT=2.35minutes; 1H NMR [(CD3)2SO)]: δ 11.8 (1H, s), 8.0 (1H, s), 7.8 (1H, d), 7.6 (d, 1H), 7.4 (1H, s), 7.2 (1H, d), 7.0 (d, 1H), 6.8 (2H, m), 6.6 (2H,m).