Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: COC1C=C(OC)C=CC=1C[NH:6][C:7]([C:9]1([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)[CH2:11][CH2:10]1)=[O:8].C(O)(C(F)(F)F)=O>>[F:18][C:15]1[CH:14]=[CH:13][C:12]([C:9]2([C:7]([NH2:6])=[O:8])[CH2:11][CH2:10]2)=[CH:17][CH:16]=1
Reactant: COc1ccc(CNC(=O)C2(c3ccc(F)cc3)CC2)c(OC)c1
Solvent: O=C(O)C(F)(F)F
Product: NC(=O)C1(c2ccc(F)cc2)CC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 81.5 %

Procedure:
A mixture of N-(2,4-dimethoxybenzyl)-1-(4-fluorophenyl)cyclopropanecarboxamide (1.5 g, 4.55 mmol) and TFA (7.02 mL, 91 mmol) was stirred at rt for 2 h. The reaction mixture was concentrated under vacuum. The residue was suspended in EtOAc (20 mL) and sat'd aqueous sodium bicarbonate (20 mL). The suspension was filtered and the filter cake was washed with EtOAc. The EtOAc layer of the filtrate was separated and the aqueous layer was extracted with ethyl acetae (2×10 mL). The combined EtOAc layers layers were washed with aqueous sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated. The residue was triturated with a minimum amount of MeOH to give 1-(4-fluorophenyl)cyclopropanecarboxamide (0.7 g, 3.71 mmol, 81% yield) as white solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 7.48-7.37 (m, 2H), 7.12-7.02 (m, 2H), 5.70 (br. s., 1H), 5.28 (br. s., 1H), 1.63 (q, J=3.8 Hz, 2H), 1.07 (q, J=3.8 Hz, 2H). LCMS: M+1=180.0.
Reaction SMILES: [F:1][C:2]1[CH:14]=[CH:13][C:5]2[NH:6]C(=O)[NH:8][S:9](=[O:11])(=[O:10])[C:4]=2[CH:3]=1.[OH-].[Na+]>S(=O)(=O)(O)O>[NH2:6][C:5]1[CH:13]=[CH:14][C:2]([F:1])=[CH:3][C:4]=1[S:9]([NH2:8])(=[O:11])=[O:10]
Reactant: O=C1Nc2ccc(F)cc2S(=O)(=O)N1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: Nc1ccc(F)cc1S(N)(=O)=O
Temperature: 130 °C
Reaction time: 1 h

Procedure:
After suspending 7-fluoro-2H,4H-benzo[e]1,2,4-thiadiazine-1,1,3-trione (3.00 g, 13.9 mmol) in 50% sulfuric acid (90 mL), the mixture was stirred at 130° C. for 1 hour. The reaction mixture was cooled in an ice bath while adding 40% aqueous sodium hydroxide for neutralization. The aqueous solution was concentrated under reduced pressure to 200 mL, and the precipitate was filtered out. It was then suspended in ethyl acetate (100 mL), and the insoluble portion was filtered out. The filtrate was concentrated under reduced pressure and dried to obtain 2-amino-5-fluorobenzenesulfonamide.
Reaction SMILES: [H-].[Na+].Cl[C:4]1[N:5]([CH2:12][CH2:13][CH:14]([OH:41])[CH2:15][O:16][C:17]2[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][CH:26]([O:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=4)[CH2:25][CH2:24]3)=[CH:19][CH:18]=2)[CH:6]=[C:7]([N+:9]([O-:11])=[O:10])[N:8]=1.[Cl-].[NH4+]>CN(C)C=O>[N+:9]([C:7]1[N:8]=[C:4]2[N:5]([CH:6]=1)[CH2:12][CH2:13][CH:14]([CH2:15][O:16][C:17]1[CH:22]=[CH:21][C:20]([N:23]3[CH2:28][CH2:27][CH:26]([O:29][C:30]4[CH:35]=[CH:34][C:33]([O:36][C:37]([F:40])([F:39])[F:38])=[CH:32][CH:31]=4)[CH2:25][CH2:24]3)=[CH:19][CH:18]=1)[O:41]2)([O-:11])=[O:10]
Reactant: O=[N+]([O-])c1cn(CCC(O)COc2ccc(N3CCC(Oc4ccc(OC(F)(F)F)cc4)CC3)cc2)c(Cl)n1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: CN(C)C=O
Product: O=[N+]([O-])c1cn2c(n1)OC(COc1ccc(N3CCC(Oc4ccc(OC(F)(F)F)cc4)CC3)cc1)CC2
Temperature: 25 °C
Reaction time: 72 h
Yield: 18.8 %

Procedure:
60% sodium hydride (70 mg) was added to an N,N-dimethylformamide solution (10 ml) of 4-(2-chloro-4-nitroimidazol-1-yl)-1-{4-[4-(4-trifluoromethoxyphenoxy)piperidin-1-yl]phenoxy}butan-2-ol (0.9 g) under ice cooling, and the mixture was stirred at room temperature for 3 days. A saturated ammonium chloride aqueous solution was added to the reaction mixture, followed by extraction with ethyl acetate. The organic layer was washed with a saturated sodium chloride aqueous solution and dried over sodium sulfate. After filtering, the filtrate was concentrated under reduced pressure. The residue thus obtained was purified by silica gel column chromatography (methylene chloride:ethyl acetate=8:2→methylene chloride:ethyl acetate=2:8) and recrystallized from methylene chloride-ethyl acetate-isopropyl ether to afford the title compound as a pale yellow powder (158 mg).
Reaction SMILES: [CH:1]1([C:4]2[C:5]([O:13][C@@H:14]([CH3:19])[C:15]([F:18])([F:17])[F:16])=[CH:6][C:7]([C:10]([OH:12])=O)=[N:8][CH:9]=2)[CH2:3][CH2:2]1.[NH2:20][C:21]([CH:31]1[CH2:33][CH2:32]1)([CH3:30])[CH2:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>>[CH:31]1([C:21]([NH:20][C:10]([C:7]2[CH:6]=[C:5]([O:13][C@@H:14]([CH3:19])[C:15]([F:18])([F:17])[F:16])[C:4]([CH:1]3[CH2:2][CH2:3]3)=[CH:9][N:8]=2)=[O:12])([CH3:30])[CH2:22][C:23]([O:25][C:26]([CH3:28])([CH3:27])[CH3:29])=[O:24])[CH2:33][CH2:32]1
Reactant: C[C@H](Oc1cc(C(=O)O)ncc1C1CC1)C(F)(F)F
Reactant: CC(C)(C)OC(=O)CC(C)(N)C1CC1
Product: C[C@H](Oc1cc(C(=O)NC(C)(CC(=O)OC(C)(C)C)C2CC2)ncc1C1CC1)C(F)(F)F

Procedure:
The title compound was synthesized in analogy to Example 112e, using 5-Cyclopropyl-4-((S)-2,2,2-trifluoro-1-methyl-ethoxy)-pyridine-2-carboxylic acid (example 68a) and tert-butyl 3-amino-3-cyclopropyl-butanoate (example 229b) as starting materials and isolated (467 mg, 56%); MS (ESI, m/z): 457.6 (M+H+).
Reaction SMILES: [CH:1]1([CH2:4][C:5]2[C:31]([OH:32])=[C:30]([C:33]([NH:35][CH3:36])=[O:34])[CH:29]=[CH:28][C:6]=2[O:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[C:13]([CH2:25][CH2:26][CH3:27])=[C:14]([CH:22]=[CH:23][CH:24]=2)[O:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:3][CH2:2]1.[CH3:37]OS(OC)(=O)=O.[OH-].[K+]>C1COCC1>[CH:1]1([CH2:4][C:5]2[C:31]([O:32][CH3:37])=[C:30]([C:33]([NH:35][CH3:36])=[O:34])[CH:29]=[CH:28][C:6]=2[O:7][CH2:8][CH2:9][CH2:10][O:11][C:12]2[C:13]([CH2:25][CH2:26][CH3:27])=[C:14]([CH:22]=[CH:23][CH:24]=2)[O:15][CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:3][CH2:2]1
Reactant: CCCc1c(OCCCOc2ccc(C(=O)NC)c(O)c2CC2CC2)cccc1OCC(=O)OCC
Reactant: COS(=O)(=O)OC
Agent: [K+]
Agent: [OH-]
Solvent: C1CCOC1
Product: CCCc1c(OCCCOc2ccc(C(=O)NC)c(OC)c2CC2CC2)cccc1OCC(=O)OCC

Procedure:
The compound of Example 63 is methylated (Me2SO4, KOH, THF) under the conditions described in Example 45. Chromatographic purification of the crude product on silica gel (Ethyl acetate/hexane (3:7) as eluant) affords the product.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH:8]=[CH:7]2)([O-])=O.ClCCl.CO.N>C1COCC1>[NH2:1][C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[N:9]([CH2:13][CH2:14][N:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1)[CH:8]=[CH:7]2
Reactant: O=[N+]([O-])c1ccc2c(ccn2CCN2CCCC2)c1
Agent: N
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CO
Product: Nc1ccc2c(ccn2CCN2CCCC2)c1

Procedure:
Prepared analogously to Example VI.1.d from 27.0 g (104 mmol) of 5-nitro-1-(2-pyrrolidin-1-ylethyl)-1H-indole (VII.1.a) in THF as solvent. Yield: 23.2 g (97% of theory); Rf value: 0.50 (silica gel, dichloromethane/methanol/ammonia=9:1:0.1); C14H19N3; EII mass spectrum: m/z=230 [M+H]+.
Reaction SMILES: [N:1]1[N:2]=[N:3][N:4]2[CH:9]=[C:8]([C@@H:10]3[CH2:12][O:11]3)[CH:7]=[CH:6][C:5]=12.[CH3:13][C@H:14]([CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1)[NH2:15]>C(O)C>[CH3:13][C@@H:14]([NH:15][CH2:12][C@@H:10]([C:8]1[CH:7]=[CH:6][C:5]2[N:4]([N:3]=[N:2][N:1]=2)[CH:9]=1)[OH:11])[CH2:16][C:17]1[C:25]2[C:20](=[CH:21][CH:22]=[CH:23][CH:24]=2)[NH:19][CH:18]=1
Reactant: C[C@@H](N)Cc1c[nH]c2ccccc12
Reactant: c1cc2nnnn2cc1[C@@H]1CO1
Solvent: CCO
Product: C[C@H](Cc1c[nH]c2ccccc12)NC[C@H](O)c1ccc2nnnn2c1

Procedure:
A solution of 325 mg of (R)-2-(tetrazolo[1,5-a]pyrid-6-yl)oxirane and 300 mg of (R)-α-methyltryptamine in 6 ml of absolute ethanol is heated at reflux under nitrogen for two hours. The reaction mixture is concentrated and the residue purified by silica gel chromatography to give (R)-α-[[(1(R)-methyl-2-(1H-indol-3-yl)ethyl)amino]-methyl]tetrazolo[1,5-a]pyridine-6-methanol.
Reaction SMILES: [CH:1]([C:4]1[N:9]=[C:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=2)[N:7]=[C:6]([OH:19])[CH:5]=1)([CH3:3])[CH3:2].[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][CH:22]=1>>[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25][O:19][C:6]2[CH:5]=[C:4]([CH:1]([CH3:3])[CH3:2])[N:9]=[C:8]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([N+:16]([O-:18])=[O:17])[CH:11]=3)[N:7]=2)=[CH:23][CH:22]=1
Reactant: Fc1ccc(CBr)cc1
Reactant: CC(C)c1cc(O)nc(-c2cccc([N+](=O)[O-])c2)n1
Product: CC(C)c1cc(OCc2ccc(F)cc2)nc(-c2cccc([N+](=O)[O-])c2)n1

Procedure:
The title compound was prepared from 6-isopropyl-2-(3-nitro-phenyl)-pyrimidin-4-ol (which was obtained in Intermediate 8) and 4-fluorobenzyl bromide according to Method A; LC retention time 4.01 min: MS: m/z (ESI) 368 (M+H)
Reaction SMILES: [C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][CH2:9][NH2:10])([CH3:4])([CH3:3])[CH3:2].[F:12][C:13]1[CH:14]=[C:15]([CH2:20][CH:21]=O)[CH:16]=[CH:17][C:18]=1[F:19].C(O)(=O)C.C([BH3-])#N.[Na+]>CO>[C:1]([O:5][C:6](=[O:11])[NH:7][CH2:8][CH2:9][NH:10][CH2:21][CH2:20][C:15]1[CH:16]=[CH:17][C:18]([F:19])=[C:13]([F:12])[CH:14]=1)([CH3:4])([CH3:2])[CH3:3]
Reactant: O=CCc1ccc(F)c(F)c1
Reactant: CC(C)(C)OC(=O)NCCN
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CO
Product: CC(C)(C)OC(=O)NCCNCCc1ccc(F)c(F)c1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 35 %

Procedure:
To a solution of tert-butyl-N-(2-aminoethyl)carbamate (718 mg, 4.5 mmol) in MeOH (40 mL) at 0° C., under nitrogen, was added (3,4-difluorophenyl)acetaldehyde (0.7 g, 4.5 mmol) in MeOH (10 mL), acetic acid (0.78 mL, 13.5 mmol) and sodium cyanoborohydride (564 mg, 9.0 mmol). After stirring at 0° C. for 15 min the cooling bath was removed and the mixture stirred at room temperature for 3 h. Saturated K2CO3 solution (50 mL) was added and the mixture stirred for a further 15 min. The solvents were removed in vacuo and the residue partitioned between water (50 mL) and EtOAc (2×50 mL). The combined organic layers were dried (Na2SO4), and evaporated. The residue was chromatographed on silica gel, eluting with CH2Cl2 :MeOH:NH3 (90:10:1) to give the amine (473 mg, 35%) as a yellow oil. 1H NMR (250 MHz, CDCl3) δ 1.44 (9H, s), 2.72-2.78 (4H, m), 2.83-2.90 (2H, m), 3.18-3.28 (2H, m), 4.87 (1H, br s), 6.87-7.13 (3H, m). MS (ES+) (301, M+1).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([C:20]([NH2:22])=[O:21])[CH:19]=2)[NH:16][N:15]=[C:14]3[CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2].C(N(C(C)C)CC)(C)C.[CH3:38][N:39]1[CH:43]=[C:42]([S:44](Cl)(=[O:46])=[O:45])[N:41]=[C:40]1[CH3:48]>CN(C1C=CN=CC=1)C>[C:1]([NH:4][C:5]1[CH:6]=[C:7]([C:11]2[CH:12]=[C:13]3[C:17](=[C:18]([C:20]([NH2:22])=[O:21])[CH:19]=2)[NH:16][N:15]=[C:14]3[CH:23]2[CH2:28][CH2:27][N:26]([S:44]([C:42]3[N:41]=[C:40]([CH3:48])[N:39]([CH3:38])[CH:43]=3)(=[O:46])=[O:45])[CH2:25][CH2:24]2)[CH:8]=[CH:9][CH:10]=1)(=[O:3])[CH3:2]
Reactant: Cc1nc(S(=O)(=O)Cl)cn1C
Reactant: CC(=O)Nc1cccc(-c2cc(C(N)=O)c3[nH]nc(C4CCNCC4)c3c2)c1
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Product: CC(=O)Nc1cccc(-c2cc(C(N)=O)c3[nH]nc(C4CCN(S(=O)(=O)c5cn(C)c(C)n5)CC4)c3c2)c1
Yield: 26.7 %

Procedure:
Following the general procedure of Example 11, 5-[3-(acetylamino)phenyl]-3-(4-piperidinyl)-1H-indazole-7-carboxamide (Example 69) (0.07 mmol), diisopropylethylamine (100 uL, 0.56 mmol), DMAP (25 mg, 0.014 mmol) and 1,2-dimethyl-1H-imidazole-4-sulfonyl chloride (33 mg, 0.17 mmol) were reacted to give the title compound (10 mg, 27% for 3 steps).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([OH:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].Cl[C:18]1[C:23]([C:24](=[O:26])[CH3:25])=[C:22]([NH:27][C:28]2[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:36])=[O:35])=[CH:32][CH:33]=2)[N:21]=[CH:20][N:19]=1>CN(C)C(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([O:14][C:18]2[C:23]([C:24](=[O:26])[CH3:25])=[C:22]([NH:27][C:28]3[CH:29]=[N:30][C:31]([S:34]([CH3:37])(=[O:35])=[O:36])=[CH:32][CH:33]=3)[N:21]=[CH:20][N:19]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(O)CC1
Reactant: CC(=O)c1c(Cl)ncnc1Nc1ccc(S(C)(=O)=O)nc1
Agent: [H-]
Agent: [Na+]
Solvent: CC(=O)N(C)C
Product: CC(=O)c1c(Nc2ccc(S(C)(=O)=O)nc2)ncnc1OC1CCN(C(=O)OC(C)(C)C)CC1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 50.4 %

Procedure:
4-Hydroxy-piperidine-1-carboxylic acid tert-butyl ester (3.2 mmol, 633 mg) and sodium hydride (3.2 mmol, 76 mg) were dissolved in N,N-dimethyl acetamide (1.5 mL) and stirred for 30 minutes at room temperature. Subsequently, compound 1-[4-chloro-6-(6-methanesulfonyl-pyridin-3-ylamino)-pyrimidin-5-yl]-ethanone (0.63 mmol, 207 mg) was added. The reaction was stirred at 70° C. for 30 minutes. Progress of the reaction was monitored by thin layer chromatography and LCMS. Sodium hydride was carefully quenched with water and the desired compound was extracted with ethyl acetate. Organic solvents were evaporated in vacuo and purified by flash chromatography (Silica gel 60; 50/50 EtoAc/Hexanes) to afford Compound A37 as a yellow solid (156 mg, 50%). 1H NMR (400 MHz, CDCl3) δ (ppm): 12.19 (s, 1H), 8.95 (s, 1H), 8.56 (d, 1H), 8.44 (s, 1H), 8.07 (d, 1H), 5.56 (h, 1H), 3.82 (m, 2H), 3.31 (m, 2H), 3.23 (s, 3H), 2.70 (s, 3H), 2.11 (m, 2H), 1.85 (m, 2H), 1.48 (s, 9H). LCMS (ESI), m/z 492.4 (M+H+, 100%).
Reaction SMILES: [NH2:1][CH2:2][CH2:3][C:4]1[N:5]([CH:27]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:6]2[C:11]([C:12]=1[CH2:13][CH2:14][O:15][C:16]1[CH:25]=[CH:24][C:19]([C:20]([O:22]C)=[O:21])=[CH:18][CH:17]=1)=[CH:10][C:9]([Cl:26])=[CH:8][CH:7]=2.[F:40][C:41]([F:47])([F:46])[S:42](Cl)(=[O:44])=[O:43]>>[CH:27]([N:5]1[C:6]2[C:11](=[CH:10][C:9]([Cl:26])=[CH:8][CH:7]=2)[C:12]([CH2:13][CH2:14][O:15][C:16]2[CH:17]=[CH:18][C:19]([C:20]([OH:22])=[O:21])=[CH:24][CH:25]=2)=[C:4]1[CH2:3][CH2:2][NH:1][S:42]([C:41]([F:47])([F:46])[F:40])(=[O:44])=[O:43])([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1)[C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1
Reactant: COC(=O)c1ccc(OCCc2c(CCN)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1
Reactant: O=S(=O)(Cl)C(F)(F)F
Product: O=C(O)c1ccc(OCCc2c(CCNS(=O)(=O)C(F)(F)F)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1
Yield: 49 %

Procedure:
To the methyl 4-{2-[2-(2-aminoethyl)-1-benzhydryl-5-chloro-1H-indol-3-yl]ethoxy}benzoate (Step 5, Example 1 )was added trifluoromethylsulfonyl chloride according to the procedure in Example 1 Step 7 to generate the product in 49% yield.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][NH:8][C:9]=2[CH:10]=1.I[CH:16]([CH3:18])[CH3:17].[H-].[Na+]>CN(C=O)C.O>[Br:1][C:2]1[CH:3]=[C:4]([C:11]([O:13][CH3:14])=[O:12])[C:5]2[CH:6]=[CH:7][N:8]([CH:16]([CH3:18])[CH3:17])[C:9]=2[CH:10]=1
Reactant: CC(C)I
Reactant: COC(=O)c1cc(Br)cc2[nH]ccc12
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COC(=O)c1cc(Br)cc2c1ccn2C(C)C
Temperature: 25 °C
Reaction time: 18 h
Yield: 55.7 %

Procedure:
To a stirred solution of methyl 6-bromo-1H-indole-4-carboxylate (100 g, 393.7 mmol) in DMF (800 mL) was added 2-iodopropane (160 g, 944.8 mmol) followed by portionwise addition of sodium hydride (20.4 g, 511.8 mmol) at 0° C. The reaction mixture was stirred at room temperature for 18 h. Diluted the reaction mixture with cold water and extracted with ethylacetate (200 mL×4), finally organic layer was washed with cold water, brine solution dried over anhydrous Na2SO4 and concentrated under reduced pressure to afford crude, which was purified by column chromatography using silica gel (60-120 mesh) with 5% EtOAC: pet ether as an eluent to afford methyl 6-bromo-1-isopropyl-1H-indole-4-carboxylate (65 g, 55.7%) as a solid. 1H NMR (CDCl3, 400 MHz) δ 1.53 (d, 6H, J=6.4 Hz), 3.973 (s, 3H), 4.598-4.664 (m, 1H), 7.111 (d, 1H, J=2.4 Hz), 7.338 (d, 1H, J=2.8 Hz), 7.711 (s, 1H), 7.987 (s, 1H).
Reaction SMILES: [CH2:1]([O:8][C@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[O:12][CH:10]1[OH:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].C([O:51][C:52](=[O:55])[CH2:53]Cl)(C)(C)C.COC(C)(C)C>[Cl-].C([N+](CCCC)(CCCC)CCCC)CCC.C(OCOCC)C>[CH2:1]([O:8][C@H:9]1[C@@H:15]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[C@H:14]([O:24][CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[C@@H:13]([CH2:32][O:33][CH2:34][C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[O:12][CH:10]1[O:11][CH2:53][C:52]([OH:55])=[O:51])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: OC1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Reactant: CC(C)(C)OC(=O)CCl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=C([O-])[O-]
Agent: [Cl-]
Solvent: COC(C)(C)C
Solvent: CCOCOCC
Product: O=C(O)COC1O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@@H]1OCc1ccccc1
Temperature: 0 °C

Procedure:
A mixture that consists of 54.1 g (100 mmol) of 2,3,4,6-tetra-O-benzyl-mannopyranose, 1.39 g (5 mmol) of tetrabutylammonium chloride and 15.2 g (110 mmol) of anhydrous potassium carbonate in 500 ml of diethoxymethane is cooled to 0° C. At 0° C., 30.12 g (200 mmol) of chloroacetic acid-tert-butyl ester is added in drops over 20 minutes while being stirred vigorously. It is stirred for one hour at 10° C. 250 ml of methyl-tert-butyl ether is added, the organic phase is separated, and the aqueous phase is extracted twice with 250 ml of water. The solvent of the combined organic phases is washed with water, dried on sodium sulfate, filtered off and distilled off in a vacuum. The residue is taken up in 500 ml of ethanol. 40 ml of 50% aqueous sodium hydroxide solution is added, and it is refluxed for 0.5 hour. It is cooled to 0° C., set at pH 8 with 10% aqueous hydrochloric acid, and then the solvent is distilled off (vacuum). The residue is taken up in 300 ml of water and 500 ml of ethyl acetate, and the pH of the aqueous phase is set at 2 while being stirred (10% aqueous hydrochloric acid). The organic phase is separated, and the aqueous phase is extracted once more with 200 ml of ethyl acetate. The combined organic phases are dried on magnesium sulfate, the solvent is distilled off in a vacuum, and the residue is chromatographed on silica gel (mobile solvent: dichloromethane/n=hexane/ethanol/acetic acid=20:5:3:0.5). The product-containing fractions are concentrated by evaporation, dissolved in 400 ml of ethyl acetate and shaken out three times with 200 ml of water. Then, the organic phase is separated and evaporated to the dry state in a vacuum.
Reaction SMILES: I[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[OH:11].N1CCC[C@H]1CO.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:38]([C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)#[CH:39]>[Pd].O.[Cu](I)I.C(OCC)(=O)C>[N+:8]([C:6]1[CH:5]=[CH:4][C:3]2[O:11][C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)=[CH:39][C:2]=2[CH:7]=1)([O-:10])=[O:9]
Reactant: O=[N+]([O-])c1ccc(O)c(I)c1
Reactant: C#Cc1ccccc1
Agent: I[Cu]I
Agent: [Pd]
Agent: OC[C@@H]1CCCN1
Solvent: CCOC(C)=O
Solvent: O
Product: O=[N+]([O-])c1ccc2oc(-c3ccccc3)cc2c1
Temperature: 80 °C
Yield: 29.6 %

Procedure:
A solution of 2-iodo-4-nitrophenol (500 mg, 1.89 mmol), prolinol (573 mg, 5.66 mmol), palladium on carbon (60 mg, 0.06 mmol), triphenylphosphine (59.4 mg, 0.226 mmol) and copper iodide (22 mg, 0.113 mmol) in water (6 mL) was stirred for 1 h at room temperature. Ethynylbenzene (482 mg, 4.72 mmol) was slowly added, and the resulting mixture was heated at 80° C. for 3 h. After cooling, ethyl acetate was added, and the mixture was passed through a pad of Celite®. The filtrate was washed with water; the combined organic layers were dried over anhydrous MgSO4 and evaporated. The resulting material was purified by column chromatography eluting with ethyl acetate/hexanes 1:40 v/v to afford 134 mg (30%) of the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([O:9][CH3:10])[C:4]=1[C:11]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([C:22](=[O:31])[N:23]([CH3:30])[CH2:24][CH2:25][CH2:26][N:27]([CH3:29])[CH3:28])=[CH:18][C:17]=2[CH:32]([CH3:34])[CH3:33])[N:14]=[C:13]([C:35]([NH:37][C:38]2([C:48]([OH:50])=[O:49])[CH:45]3[CH2:46][CH:41]4[CH2:42][CH:43]([CH2:47][CH:39]2[CH2:40]4)[CH2:44]3)=[O:36])[CH:12]=1.CC([O-])(C)C.[K+:56]>CC(O)C>[K+:56].[CH3:10][O:9][C:5]1[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[C:4]=1[C:11]1[N:15]([C:16]2[CH:21]=[CH:20][C:19]([C:22](=[O:31])[N:23]([CH3:30])[CH2:24][CH2:25][CH2:26][N:27]([CH3:28])[CH3:29])=[CH:18][C:17]=2[CH:32]([CH3:34])[CH3:33])[N:14]=[C:13]([C:35]([NH:37][C:38]2([C:48]([O-:50])=[O:49])[CH:39]3[CH2:40][CH:41]4[CH2:42][CH:43]([CH2:44][CH:45]2[CH2:46]4)[CH2:47]3)=[O:36])[CH:12]=1
Reactant: COc1cccc(OC)c1-c1cc(C(=O)NC2(C(=O)O)C3CC4CC(C3)CC2C4)nn1-c1ccc(C(=O)N(C)CCCN(C)C)cc1C(C)C
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: CC(C)O
Product: COc1cccc(OC)c1-c1cc(C(=O)NC2(C(=O)[O-])C3CC4CC(C3)CC2C4)nn1-c1ccc(C(=O)N(C)CCCN(C)C)cc1C(C)C
Temperature: -20 °C
Yield: 56.8 %

Procedure:
A solution of 0.15 g of the compound obtained in EXAMPLE 1' and 0.03 g of potassium tert-butylate in 6.5 ml of 2-propanol is left overnight at RT and then concentrated under vacuum. The residue is dissolved in 0.5 ml of MeOH, and this solution is poured into 25 ml of isopropyl ether cooled to -20° C. The precipitate formed is drained and dried over P2O5 at 80° C. 0.09 g of the expected product is obtained, m.p.=222° C.
Reaction SMILES: [NH2:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[C:8]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=4)[CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1.[CH3:26][N:27]([CH3:34])[CH2:28][CH2:29][CH2:30][C:31](O)=[O:32]>>[CH3:26][N:27]([CH3:34])[CH2:28][CH2:29][CH2:30][C:31]([NH:1][C:2]1[CH:14]=[C:13]2[C:5]([C:6]3[CH:7]=[C:8]([C:18]4[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[CH:19]=4)[CH:9]=[C:10]([C:15]([NH2:17])=[O:16])[C:11]=3[NH:12]2)=[CH:4][CH:3]=1)=[O:32]
Reactant: COc1cccc(-c2cc(C(N)=O)c3[nH]c4cc(N)ccc4c3c2)c1
Reactant: CN(C)CCCC(=O)O
Product: COc1cccc(-c2cc(C(N)=O)c3[nH]c4cc(NC(=O)CCCN(C)C)ccc4c3c2)c1

Procedure:
This was similarly prepared from 7-amino-3-(3-methoxyphenyl)-9H-carbazole-1-carboxamide and 4-(dimethylamino)butanoic acid. MS (ESI) m/z 445.26 (M+H). 1H NMR (500 MHz, MeOD) δ ppm 8.45 (1H, d, J=1.83 Hz), 8.14 (1H, d, J=1.53 Hz), 8.10 (1H, d, J=8.55 Hz), 8.05 (1H, d, J=1.83 Hz), 7.35-7.39 (3H, m), 7.29 (1H, dd, J=8.39, 1.68 Hz), 6.93 (1H, dt, J=7.55, 2.02 Hz), 3.91 (3H, s), 2.54-2.61 (2H, m), 2.50 (2H, t, J=7.32 Hz), 2.40 (6H, s), 1.91-2.02 (2H, m).
Reaction SMILES: [CH2:1]([C:8]1[O:9][C:10]2[CH:29]=[CH:28][CH:27]=[CH:26][C:11]=2[C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[O:31][C:32](=[O:42])[CH:33]([CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)O>>[CH2:1]([C:8]1[O:9][C:10]2[CH:29]=[CH:28][CH:27]=[CH:26][C:11]=2[C:12]=1[C:13]1[CH:18]=[CH:17][C:16]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH:33]([CH2:35][C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:32]([OH:42])=[O:31])=[CH:21][CH:20]=2)=[CH:15][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1ccc(-c2ccc(-c3c(Cc4ccccc4)oc4ccccc34)cc2)cc1
Reactant: COC(=O)C(O)Cc1ccccc1
Product: O=C(O)C(Cc1ccccc1)Oc1ccc(-c2ccc(-c3c(Cc4ccccc4)oc4ccccc34)cc2)cc1

Procedure:
The title compound was prepared from 4′-(2-benzyl-benzofuran-3-yl)-biphenyl-4-ol, and 3-phenyllactic acid methyl ester, in substantially the same manner, as described in Example 1, steps g-h , and was obtained as a white solid, mp 164-166° C.; MS m/e 524 (M+);