Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[CH:3]1[CH2:8][NH:7][C:6](=[O:9])[NH:5][C:4]1=[O:10].II.S(=O)(=O)(O)O.S([O-])([O-])=O.[Na+].[Na+]>CS(C)=O>[F:11][C:2]([F:1])([F:12])[C:3]1[C:4](=[O:10])[NH:5][C:6](=[O:9])[NH:7][CH:8]=1
Reactant: O=C1NCC(C(F)(F)F)C(=O)N1
Agent: II
Agent: O=S(=O)(O)O
Agent: O=S([O-])[O-]
Solvent: CS(C)=O
Product: O=c1[nH]cc(C(F)(F)F)c(=O)[nH]1
Temperature: 140 °C
Reaction time: 6 h
Yield: 87.9 %

Procedure:
In 88.7 ml of dimethylsulfoxide, 25.2 g of 5-trifluoromethyl-5,6-dihydrouracil was dissolved and 3.47 g of iodine and 0.76 ml of concentrated sulfuric acid were added to the solution to obtain a uniform solution. The obtained solution was stirred at 140° C. for 6 hours, and then cooled to room temperature, followed by adding 150 g of 3% aqueous sodium sulfite solution to reduce iodine. The resulting mixture was concentrated under reduced pressure. After adding water to the residue, the residue was extracted three times with ethyl acetate. The ethyl acetate layer was concentrated and the residue was recrystallized from 1.00 ml of water to obtain 21.9 g (88%) of 5-trifluoromethyluracil as white needle-shaped crystals.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[NH:8][N:9]=[C:10]([I:11])[C:5]2=[CH:4][CH:3]=1.[O:12]1[CH:17]=[CH:16][CH2:15][CH2:14][CH2:13]1.CS(O)(=O)=O>C(Cl)Cl.O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]2[N:8]([CH:13]3[CH2:14][CH2:15][CH2:16][CH2:17][O:12]3)[N:9]=[C:10]([I:11])[C:5]2=[CH:4][CH:3]=1
Reactant: C1=COCCC1
Reactant: Clc1ccc2c(I)n[nH]c2n1
Agent: CS(=O)(=O)O
Solvent: C1CCOC1
Solvent: ClCCl
Product: Clc1ccc2c(I)nn(C3CCCCO3)c2n1
Temperature: 25 °C
Reaction time: 8 h
Yield: 88 %

Procedure:
A mixture of 6-chloro-3-iodo-1H-pyrazolo[3,4-b]pyridine (0.70 g, 2.5 mmol), dihydropyran (690 μL, 7.5 mmol) and methanesulfonic acid (33 μL, 0.50 mmol) in methylene chloride (30 mL) and tetrahydrofuran (10 mL) in reaction flask was stirred at r.t. overnight. It was concentrated under reduced pressure. The residue was purified by flash chromatography on a silica gel column with ethyl acetate in hexanes (0-50%) to afford the desired product (0.80 g). LCMS (M-84+H)+=279.9.
Reaction SMILES: Br[C:2]([F:6])=[C:3]([F:5])[F:4].C(=O)=O.[CH3:10][O:11][CH2:12][CH2:13][CH:14]([C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)Br>CN(C)C=O.CC1CC[C@@H](C(C)=C)CC=1.[Zn]>[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([CH:14]([CH2:13][CH2:12][O:11][CH3:10])[C:2]([F:6])=[C:3]([F:5])[F:4])=[CH:21][CH:20]=1
Reactant: COCCC(Br)c1ccc(Cl)cc1
Reactant: FC(F)=C(F)Br
Agent: C=C(C)[C@H]1CC=C(C)CC1
Agent: O=C=O
Agent: [Zn]
Solvent: CN(C)C=O
Product: COCCC(C(F)=C(F)F)c1ccc(Cl)cc1
Temperature: 60 °C
Reaction time: 0.5 h
Yield: 13.1 %

Procedure:
Bromotrifluoroethylene (41.5 g, 257 mmol) was distilled (dry ice condenser) into a flask containing zinc (13.6 g, 208 mmol) and N,N-dimethylformamide (153 ml), and the resulting mixture was heated at approximately 60° C. for two hours. The reaction mixture was purged with nitrogen for one hour, cooled to −8° C., treated with cuprous bromide (29.83 g, 208 mmol), and stirred for 30 minutes without external cooling. 3-(4-chlorophenyl)-3-bromopropyl methyl ether (17.06 g, 64.7 mmol) in N,N-dimethylformamide (10 ml) was added followed by limonene (5 drops), and the resulting mixture was heated at 50° C. for 8 hours. The cooled reaction mixture was quenched with aqueous ammonium chloride and thoroughly extracted with hexane. The combined organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuo to a brown oil (10.76 g). Chromatography on silica gel eluting with methylene chloride:hexane (1:9) afforded the title compound as a yellow oil (2.25 g), which was characterized by IR, 1HNMR and mass spectral analysis.
Reaction SMILES: C([O:3][C:4]([C:6]1([NH:17][C:18]([C:20]2[C:29]3[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=3[CH:23]=[CH:22][CH:21]=2)=[O:19])[CH2:14][C:13]2[C:8](=[CH:9][C:10]([CH3:16])=[C:11]([CH3:15])[CH:12]=2)[CH2:7]1)=[O:5])C.[OH-].[K+].O>CCO>[CH3:15][C:11]1[CH:12]=[C:13]2[C:8](=[CH:9][C:10]=1[CH3:16])[CH2:7][C:6]([NH:17][C:18]([C:20]1[C:29]3[CH2:28][CH2:27][CH2:26][CH2:25][C:24]=3[CH:23]=[CH:22][CH:21]=1)=[O:19])([C:4]([OH:5])=[O:3])[CH2:14]2
Reactant: CCOC(=O)C1(NC(=O)c2cccc3c2CCCC3)Cc2cc(C)c(C)cc2C1
Agent: [K+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: Cc1cc2c(cc1C)CC(NC(=O)c1cccc3c1CCCC3)(C(=O)O)C2
Temperature: 25 °C
Reaction time: 8 h
Yield: 96.7 %

Procedure:
The mixture of 5,6-dimethyl-2-[(5,6,7,8-tetrahydro-naphthalene-1-carbonyl)-amino]-indan-2-carboxylic acid ethyl ester (78) (438 mg, 1.11 mmol) and KOH (1 g, 18 mmol) is dissolved in EtOH (8 mL) and water (1 mL) under a water bath. The water bath is removed when KOH is completely dissolved and the resulting reaction solution is stirred at RT for 8 h. After concentration in vacuo, the residue is dissolved in water (20 mL) and acidified with conc. HCl until no more precipitate formed. The precipitate is filtered to give a pure product (79) as a pale brown solid (390 mg, 97%).
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([C:6]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].[CH:18]([C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Cl)=[CH:23][CH:22]=1)([CH3:20])[CH3:19].O>COCCOC>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6](=[O:7])[CH:8]([CH2:25][C:24]2[CH:27]=[CH:28][C:21]([CH:18]([CH3:20])[CH3:19])=[CH:22][CH:23]=2)[C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:14][CH:15]=1
Reactant: CC(C)c1ccc(CCl)cc1
Reactant: CCOC(=O)CC(=O)c1ccc(F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: COCCOC
Solvent: O
Product: CCOC(=O)C(Cc1ccc(C(C)C)cc1)C(=O)c1ccc(F)cc1
Reaction time: 0.5 h

Procedure:
To a solution of ethyl (4-fluorobenzoyl)acetate (23.21 g, 110.4 mmol) in 1,2-dimethoxyethane (150 ml) was added a suspension (4.42 g, 110 mmol) of 60% sodium hydride in liquid paraffin under ice-cooling and the mixture was stirred as it was for 0.5 hr. A solution of 4-isopropylbenzyl chloride (18.6 g 110 mmol) in 1,2-dimethoxyethane (50 ml) was added at room temperature and the mixture was stirred at 70° C. overnight. The reaction solution was poured into water and extracted twice with ethyl acetate. The collected organic layer was dried over anhydrous magnesium sulfate and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=15/1-9/1) to give the objective substance.
Reaction SMILES: C[O:2][C:3](=[O:18])[C:4]1[CH:9]=[C:8]([CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)[CH:7]=[CH:6][C:5]=1[NH2:17].[OH-].[Li+].O>C1COCC1.CO>[NH2:17][C:5]1[CH:6]=[CH:7][C:8]([CH2:10][CH2:11][N:12]2[CH2:16][CH2:15][CH2:14][CH2:13]2)=[CH:9][C:4]=1[C:3]([OH:18])=[O:2]
Reactant: COC(=O)c1cc(CCN2CCCC2)ccc1N
Agent: [Li+]
Agent: [OH-]
Solvent: CO
Solvent: O
Solvent: C1CCOC1
Product: Nc1ccc(CCN2CCCC2)cc1C(=O)O
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 2-amino-5-(2-pyrrolidin-1-yl-ethyl)-benzoic acid methyl ester (1.04 g, 4.19 mmol) in a mixture of THF (8 mL) and methanol (5 mL) was added lithium hydroxide (0.36 g), followed by water (3 mL). The reaction mixture was stirred at room temperature overnight, and then refluxed for 4 hours. After cooling to room temperature, the was solvent concentrated. The pH was adjusted to approximately 5 with 2 N aqueous hydrochloric acid and the residue was evaporated to dryness to give 2-amino-5-(2-pyrrolidin-1-yl-ethyl)-benzoic acid as a chloride salt. Yield: 1.84 g. The crude material was used in the next step without further purification.
Reaction SMILES: [CH3:1][C:2]1([OH:7])[CH2:6][CH2:5][NH:4][CH2:3]1.O[C@H]1CCNC1.[OH:14][C:15]1([CH2:22][NH:23][C:24]([C:26]2[C:27]3[CH:28]=[CH:29][C:30](Cl)=[N:31][C:32]=3[CH:33]=[CH:34][C:35]=2[Cl:36])=[O:25])[CH2:20][CH2:19][CH2:18][CH:17]([CH3:21])[CH2:16]1.C(N(C(C)C)CC)(C)C>C(#N)C.C(N(CC)CC)C>[Cl:36][C:35]1[CH:34]=[CH:33][C:32]2[N:31]=[C:30]([N:4]3[CH2:5][CH2:6][C:2]([OH:7])([CH3:1])[CH2:3]3)[CH:29]=[CH:28][C:27]=2[C:26]=1[C:24]([NH:23][CH2:22][C@:15]1([OH:14])[CH2:20][CH2:19][CH2:18][C@H:17]([CH3:21])[CH2:16]1)=[O:25]
Reactant: CC1(O)CCNC1
Reactant: CC1CCCC(O)(CNC(=O)c2c(Cl)ccc3nc(Cl)ccc23)C1
Agent: O[C@H]1CCNC1
Solvent: CCN(CC)CC
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: C[C@H]1CCC[C@@](O)(CNC(=O)c2c(Cl)ccc3nc(N4CCC(C)(O)C4)ccc23)C1

Procedure:
The title compound was prepared by the method of Example 1, step e) by reacting 3-methylpyrrolidin-3-ol (0.42 g) (instead of (S)-3-hydroxypyrrolidine) with 2,6-dichloro-quinoline-5-carboxylic acid (1-hydroxy-3-methyl-cyclohexylmethyl)-amide (0.10 g) and triethylamine (0.38 ml) (instead of diisopropylethylamine) in acetonitrile (1 ml) to afford the title compound crude and as a 1:1 mixture of diastereomers. The reaction was concentrated in vacuo and the products isolated by flash column chromatography (SiO2, 4% methanol/dichloromethane as eluent) as a colourless solid (70 mg). The diastereomers were separated by supercritical fluid chromatography (SFC) on an OJ Daicel column using 25% ethanol/carbon dioxide as eluent to afford Isomer 1 as a colourless solid (18 mg).
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH:11]([OH:16])[C:12]([F:15])([F:14])[F:13])=[CH:7][N:6]=1.O.Cl[O-].[Ca+2].Cl[O-]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)Cl>[F:18][C:2]([F:1])([F:17])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11](=[O:16])[C:12]([F:13])([F:14])[F:15])=[CH:7][N:6]=1
Reactant: OC(c1ccc(OCC(F)(F)F)nc1)C(F)(F)F
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: O=S(=O)([O-])O
Agent: [Ca+2]
Solvent: O
Solvent: ClCCl
Product: O=C(c1ccc(OCC(F)(F)F)nc1)C(F)(F)F
Reaction time: 4 h

Procedure:
2.75 g (0.01 mol) of 2-(2,2,2-trifluoroethoxy)-5-(2,2,2-trifluoro-1-hydroxyethyl)pyridine and 0.18 g (0.0005 mol) of tetrabutylammonium hydrogen sulfate are dissolved in 20 ml of methylene chloride at room temperature. After addition of 4 ml of water and 1.72 g (0.012 mol) of calcium hypochlorite the mixture is stirred for 4 hours with vigorous mixing, during which the reaction temperature rises to 25 ° C. The reaction mixture is added to 50 ml of water, the phases are separated, the aqueous phase is extracted several times with methylene chloride and the combined organic phases are washed with saturated aqueous sodium chloride solution. After drying the organic phase with sodium sulfate, the volatiles are distilled off. Following distillation of the crude product in a kugelrohr (0.3 mbar, 100°-120° C. bath temperature), 2.38 g (87% of theory) of 2-(2,2,2-trifluoroethoxy)-5-trifluoroacetylpyridine are obtained.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[NH:14][C:13]([C:18]([O:20]CC)=[O:19])=[C:12]2[C:23]1[CH:28]=[CH:27][C:26]2[O:29][CH2:30][O:31][C:25]=2[CH:24]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:32]([CH2:37][O:38][C:39]1[CH:46]=[C:45]([O:47][CH3:48])[CH:44]=[CH:43][C:40]=1[CH2:41]Cl)([O:34]CC)=[O:33]>>[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:15](=[CH:16][CH:17]=1)[N:14]([CH2:41][C:40]1[CH:43]=[CH:44][C:45]([O:47][CH3:48])=[CH:46][C:39]=1[O:38][CH2:37][C:32]([OH:34])=[O:33])[C:13]([C:18]([OH:20])=[O:19])=[C:12]2[C:23]1[CH:28]=[CH:27][C:26]2[O:29][CH2:30][O:31][C:25]=2[CH:24]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)COc1cc(OC)ccc1CCl
Reactant: CCOC(=O)c1[nH]c2ccc(OCc3ccccc3)cc2c1-c1ccc2c(c1)OCO2
Product: COc1ccc(Cn2c(C(=O)O)c(-c3ccc4c(c3)OCO4)c3cc(OCc4ccccc4)ccc32)c(OCC(=O)O)c1

Procedure:
5-Benzyloxy-1-(2-carboxymethoxy-4-methoxybenzyl)-3-(3,4-methylenedioxyohenyl)indole-2-carboxylic acid. The title compound was prepared by alkylation of ethyl 5-benzyloxy-3-(3,4-methylenedioxyphenyl)indole-2-carboxylate with 2-carboethoxymethoxy-4-methoxybenzyl chloride followed by saponification using methods previously described in examples 1c and 1d; m.p. 182°-190° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:31])([CH3:30])[CH3:29])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH2:22])[N:20]=[C:15]2[CH:14]=1.N1C=CC=CC=1.[C:38](Cl)(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1>C1COCC1.C([O-])([O-])=O.[Na+].[Na+]>[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH3:12])[CH:7]=[C:6]2[C:13]1[N:23]([CH2:24][O:25][CH2:26][CH2:27][Si:28]([CH3:30])([CH3:29])[CH3:31])[C:16]2=[N:17][CH:18]=[C:19]([CH2:21][NH:22][C:38](=[O:45])[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)[N:20]=[C:15]2[CH:14]=1
Reactant: COc1ccc2c(c1)c(-c1cc3nc(CN)cnc3n1COCC[Si](C)(C)C)cn2C
Reactant: O=C(Cl)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: c1ccncc1
Solvent: C1CCOC1
Product: COc1ccc2c(c1)c(-c1cc3nc(CNC(=O)c4ccccc4)cnc3n1COCC[Si](C)(C)C)cn2C
Temperature: 60 °C
Reaction time: 0.33 h
Yield: 77.8 %

Procedure:
(6-(5-Methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methanamine (0.095 g, 0.28 mmol, Example #20, Step G) in THF (5 mL) was treated with pyridine (0.026 ml, 0.33 mmol) and benzoyl chloride (0.033 ml, 0.28 mmol). The mixture was stirred for about 20 min at about 60° C. and cooled to ambient temperature, diluted with aqueous Na2CO3 (15 mL), and extracted with EtOAc (20 mL). The organic solution was dried over anhydrous MgSO4, filtered, and concentrated to give N-((6-(5-methoxy-1-methyl-1H-indol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)methyl)benzamide (0.118 g, 100%): LC/MS (Table 2, Method d) Rt=1.64 min; MS m/z: 542 (M+H)+.
Reaction SMILES: [Si]([O:8][C@@H:9]1[CH2:13][C@H:12]([C:14]2[N:18]3[C:19]4[CH:25]=[CH:24][N:23]([S:26]([C:29]5[CH:35]=[CH:34][C:32]([CH3:33])=[CH:31][CH:30]=5)(=[O:28])=[O:27])[C:20]=4[N:21]=[CH:22][C:17]3=[N:16][N:15]=2)[C@H:11]([CH2:36][CH3:37])[CH2:10]1)(C(C)(C)C)(C)C.Cl.CCOC(C)=O>C(O)C.C([C@H]1[C@@H](C2N3C4C=CN(S(C5C=CC(C)=CC=5)(=O)=O)C=4N=CC3=NN=2)C[C@@H](O)C1)C>[CH2:36]([CH:11]1[CH:12]([C:14]2[N:18]3[C:19]4[CH:25]=[CH:24][N:23]([S:26]([C:29]5[CH:30]=[CH:31][C:32]([CH3:33])=[CH:34][CH:35]=5)(=[O:28])=[O:27])[C:20]=4[N:21]=[CH:22][C:17]3=[N:16][N:15]=2)[CH2:13][CH:9]([OH:8])[CH2:10]1)[CH3:37]
Reactant: CC[C@@H]1C[C@H](O[Si](C)(C)C(C)(C)C)C[C@@H]1c1nnc2cnc3c(ccn3S(=O)(=O)c3ccc(C)cc3)n12
Agent: CC[C@@H]1C[C@H](O)C[C@@H]1c1nnc2cnc3c(ccn3S(=O)(=O)c3ccc(C)cc3)n12
Agent: Cl
Solvent: CCO
Solvent: CCOC(C)=O
Product: CCC1CC(O)CC1c1nnc2cnc3c(ccn3S(=O)(=O)c3ccc(C)cc3)n12
Reaction time: 1 h

Procedure:
A scalemic mixture enriched in 1-((1S,2R,4S)-4-(tert-butyldimethylsilyloxy)-2-ethylcyclopentyl)-6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (9.58 g, 17.8 mmol) was dissolved in ethanol (177 mL). Concd HCl (1.75 mL, 21.3 mmol) was added dropwise. After about 1 h, EtOAc (700 mL) was added. The organic mixture was washed with saturated aqueous NaHCO3 (2×120 mL), brine (120 mL), dried over anhydrous MgSO4, filtered and concd under reduced pressure. The residue was purified using silica gel chromatography eluting with 30-100% EtOAc in DCM to give a scalemic mixture enriched in (1S,3R,4S)-3-ethyl-4-(6-tosyl-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentanol (6.73 g, 89%): LC/MS (Table 1, Method b) Rt=2.11 min; MS m/z: 426 (M+H)+.
Reaction SMILES: Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl>Cl[Pd]Cl.O.O1CCOCC1>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:14]3[CH:15]=[CH:16][N:11]=[CH:12][CH:13]=3)[C:7]1=2
Reactant: OB(O)c1ccncc1
Reactant: Brc1cccc2ccsc12
Agent: Cl[Pd]Cl
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Solvent: ClCCl
Product: c1cc(-c2ccncc2)c2sccc2c1
Temperature: 80 °C
Reaction time: 24 h
Yield: 129 %

Procedure:
To 7-bromo--benzo[b]thiophene (5.28 g, 24.7 mmol) was added pyridine-4-boronic acid (2.734 g, 22.24 mmol), K3PO4 (12.0 g, 56.5 mmol), 37.5 mL of 1,4-dioxane and 3.8 mL of water. The mixture was placed under vacuum for several minutes and flushed with nitrogen. This was repeated 5 times. Pd(dppf)Cl2.CH2Cl2 (0.909 g, 1.11 mmol), PdCl2 (0.1994 g, 1.124 mmol) and 1,1″-bis(diphenylphosphino)ferrocene (0.6234 g, 1.124 mmol) were purged in the same way using high vacuum. The catalyst was added to the reaction flask, which was purged again 3 times. The mixture was stirred at 80° C. under nitrogen. After 1 day TLC showed much starting material remained. Additional K3PO4 (2.3 g, 10.8 mmol) was added after purging. Stirring at 80° C. under nitrogen was continued for 12 to 14 hours and then at room temperature till the next day. The mixture was partitioned between water and ethyl acetate, filtered through Celite and the layers separated. The organic layer was concentrated in vacuum. The residue was redissolved in ethyl acetate, washed with water and dried over magnesium sulfate. Concentration in vacuum gave 6.06 g of dark oil. This was eluted from silica gel with a gradient of hexane and ethyl acetate to give 2.43 g of the title compound as a tan oil that crystallizes slowly, (m.p.71-72° C.).
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[CH:4][C:3]=1[C:11]([F:14])([F:13])[F:12].[NH:15]([CH2:19][CH2:20][OH:21])[CH2:16][CH2:17][OH:18]>CS(C)=O>[F:12][C:11]([F:14])([F:13])[C:3]1[CH:4]=[C:5]([N+:8]([O-:10])=[O:9])[CH:6]=[CH:7][C:2]=1[N:15]([CH2:19][CH2:20][OH:21])[CH2:16][CH2:17][OH:18]
Reactant: O=[N+]([O-])c1ccc(F)c(C(F)(F)F)c1
Reactant: OCCNCCO
Solvent: CS(C)=O
Product: O=[N+]([O-])c1ccc(N(CCO)CCO)c(C(F)(F)F)c1
Temperature: 140 °C
Yield: 8 %

Procedure:
2-Fluoro-5-nitrobenzotrifluoride (5.0 g; 23.9 mmol) and 6.0 g (57.1 mmol) of diethanolamine were dissolved solved in 30 ml of DMSO, followed by stirring under heat at 140° C. for 5 hours. The reaction mixture was extracted with ethyl acetate and the extract was then dried over magnesium sulfate. The brown oil so obtained was purified by chromatography on a silica gel column (chloroform/ methanol=10/1), whereby 565 mg of the title compound were obtained as yellow powder (yield: 8%).
Reaction SMILES: [OH:1][CH:2]([C@H:6]1[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@H:7]1[CH2:13][O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])C(O)C.I([O-])(=O)(=O)=O.[Na+]>CC(C)=O.O>[CH:2]([C@H:6]1[O:10][C:9]([CH3:12])([CH3:11])[O:8][C@H:7]1[CH2:13][O:14][CH2:15][C:16]([O:18][CH3:19])=[O:17])=[O:1]
Reactant: COC(=O)COC[C@@H]1OC(C)(C)O[C@@H]1C(O)C(C)O
Agent: [Na+]
Agent: [O-][I+3]([O-])([O-])[O-]
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)COC[C@@H]1OC(C)(C)O[C@@H]1C=O
Reaction time: 1 h
Yield: 75.4 %

Procedure:
A solution of 2-[[(4S,5R)-5-(1,2-dihydroxypropyl)-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester (20 g, 72 mmol) in acetone (20 mL) was diluted with water (400 mL) and treated with solid sodium periodate (26.13 g, 122 mmol). The reaction was analyzed by TLC and was complete after stirring for 1 hour. The reaction mixture was extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried, and concentrated to give 12.6 g of 2-[[(4S,5S)-5-formyl-2,2-dimethyl-1,3-dioxolan-4-yl]methoxy]ethanoic acid, methyl ester, a compound of formula (M), as a slightly yellow viscous oil; 1H NMR (CDCl3) δ 1.38 (s, 3H), 1.57 (s, 3H), 3.75 (m, 2H), 3.7 (s, 3H), 4.08 (m, 2H), 4.42 (m, 1H), 4.54 (m, 1H), 9.64 (d, 1H) ppm.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.Cl.C(N=C=NCCCN(C)C)C.[CH3:19][O:20][C:21]1[C:22](=[O:45])[C:23]([CH3:44])=[C:24]([CH2:30][C:31]2[C:32]([O:40][C:41](=[O:43])[CH3:42])=[C:33]([CH:37]=[CH:38][CH:39]=2)[C:34](O)=[O:35])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]>C(Cl)Cl>[CH3:19][O:20][C:21]1[C:22](=[O:45])[C:23]([CH3:44])=[C:24]([CH2:30][C:31]2[C:32]([O:40][C:41](=[O:43])[CH3:42])=[C:33]([CH:37]=[CH:38][CH:39]=2)[C:34]([N:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)=[O:35])[C:25](=[O:29])[C:26]=1[O:27][CH3:28]
Reactant: COC1=C(OC)C(=O)C(Cc2cccc(C(=O)O)c2OC(C)=O)=C(C)C1=O
Reactant: C1CCNCC1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: ClCCl
Product: COC1=C(OC)C(=O)C(Cc2cccc(C(=O)N3CCCCC3)c2OC(C)=O)=C(C)C1=O
Temperature: 25 °C
Reaction time: 12 h
Yield: 44.1 %

Procedure:
Piperidine (0.133 g, 1.56 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.448 g, 2.34 mmol) were added to a methylene chloride solution (30 ml) of 3-(5,6-dimethoxy-3-methyl-1,4-benzoquinon-2-yl)methyl-2-acetoxybenzoic acid (0.293 g, 0.783 mmol) and the resulting solution was stirred at room temperature for 12 hours. The reaction solution was poured into ice water and then extracted with methylene chloride. The extract was washed with water and then dried, and the solvent was removed by distillation. The obtained residue was purified by preparative thin-layer chromatography (chloroform:methanol=30:1) to obtain the titled compound (0.152 g, 0.345 mmol, 44%).
Reaction SMILES: [N+:1]([C:4]1[CH:20]=[CH:19][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15](Cl)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH:21]1([NH2:27])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[N+:1]([C:4]1[CH:20]=[CH:19][C:7]([O:8][C:9]2[CH:14]=[CH:13][C:12]([S:15]([NH:27][CH:21]3[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]3)(=[O:17])=[O:16])=[CH:11][CH:10]=2)=[CH:6][CH:5]=1)([O-:3])=[O:2]
Reactant: O=[N+]([O-])c1ccc(Oc2ccc(S(=O)(=O)Cl)cc2)cc1
Reactant: NC1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: O=[N+]([O-])c1ccc(Oc2ccc(S(=O)(=O)NC3CCCCC3)cc2)cc1
Reaction time: 8 h

Procedure:
4-(4-Nitrophenoxy)benzenesulphonyl chloride (Example 1) (18.8 g), cyclohexylamine (6.5 g), anhydrous potassium carbonate (8.3 g) and acetone (100 ml) were refluxed together for 4 hours. On concentration and addition of water, an oil separated which solidified overnight. From ethanol on addition of light petroleum (b.p. 60°-80° C.), 4-(4-nitrophenoxy)-N-cyclohexylbenzenesulphonamide was obtained in the form of crystals, m.p. 94° C.
Reaction SMILES: [CH3:1][S:2](Cl)(=[O:4])=[O:3].CCN(CC)CC.[CH3:13][O:14][C:15](=[O:55])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([Cl:34])[CH:32]=3)[N:27]([CH:35]([C:42]3[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=3)[C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:26]=2[CH2:48][CH2:49][OH:50])=[CH:18][C:17]=1[O:51][CH:52]([CH3:54])[CH3:53]>ClCCl>[CH3:13][O:14][C:15](=[O:55])[C:16]1[CH:21]=[CH:20][C:19]([O:22][CH2:23][CH2:24][C:25]2[C:33]3[C:28](=[CH:29][CH:30]=[C:31]([Cl:34])[CH:32]=3)[N:27]([CH:35]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)[C:42]3[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=3)[C:26]=2[CH2:48][CH2:49][O:50][S:2]([CH3:1])(=[O:4])=[O:3])=[CH:18][C:17]=1[O:51][CH:52]([CH3:53])[CH3:54]
Reactant: COC(=O)c1ccc(OCCc2c(CCO)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1OC(C)C
Reactant: CS(=O)(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)c1ccc(OCCc2c(CCOS(C)(=O)=O)n(C(c3ccccc3)c3ccccc3)c3ccc(Cl)cc23)cc1OC(C)C
Temperature: 0 °C
Reaction time: 1 h
Yield: 100 %

Procedure:
Methane sulfonyl chloride (0.03 mL, 0.39 mmol) and Et3N (0.06 mL, 0.43 mmol) were added to a solution of the alcohol from Step 4 (0.10 g, 0.17 mmol) in dichloromethane (8 mL) at 0° C. Reaction was stirred at 0° C. for one hour and then warmed to room temperature and stirred an additional hour. Reaction solution was concentrated by rotary evaporation. Obtained 0.115 g of 4-(2-[1-Benzhydryl-5-chloro-2-(2-methanesulfonyloxy-ethyl)-1H-indol-3-yl]-ethoxy}-2-isopropoxy-benzoic acid methyl ester in quantitative yield.