Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[CH2:2][C:3](=O)[CH2:4][CH2:5][CH2:6][N:7]1[C:15](=[O:16])[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]1=[O:17].[C:19]([NH2:27])(=[NH:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[C:20]1([C:19]2[NH:26][CH:2]=[C:3]([CH2:4][CH2:5][CH2:6][N:7]3[C:15](=[O:16])[C:14]4[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=4)[C:8]3=[O:17])[N:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(CBr)CCCN1C(=O)c2ccccc2C1=O
Reactant: N=C(N)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: O=C1c2ccccc2C(=O)N1CCCc1c[nH]c(-c2ccccc2)n1
Temperature: 80 °C
Reaction time: 4 h
Yield: 67.6 %

Procedure:
To a solution of 2-(5-bromo-4-oxo-pentyl)-isoindole-1,3-dione [CAS 41306-64-3](12.4 g) in abs. DMF (50 ml) was added benzamidine 85% (5.65 g) and potassium carbonate (11.05 g). The reaction mixture was stirred at 80° C. for 4 h, concentrated under high vacuum, quenched with water and extracted with ethyl acetate. The organic phase was washed with ice/water and brine, dried over magnesium sulphate and concentrated. The residue was purified by chromatography on silica gel using methylene chloride/methanol 2 and 5% as eluent. The product fractions were combined and evaporated to dryness to obtain 2-[3-(2-phenyl-1H-imidazol-4-yl)-propyl]-isoindole-1,3-dione (8.95 g) as a light yellow foam.
Reaction SMILES: [Mg].C(O[CH:5]([O:15]CC)[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]Cl)C.Cl[CH:19]([CH2:22][CH3:23])[CH:20]=[CH2:21].ClCC=CCC.Cl>O1CCCC1.CC(C)=O.C(Cl)CCC>[CH:5](=[O:15])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:21][CH:20]=[CH:19][CH2:22][CH3:23]
Reactant: CCOC(CCCCCCCCCl)OCC
Reactant: C=CC(Cl)CC
Agent: CCC=CCCl
Agent: Cl
Agent: [Mg]
Solvent: C1CCOC1
Solvent: CCCCCl
Solvent: CC(C)=O
Product: CCC=CCCCCCCCCCC=O
Temperature: 5 °C
Reaction time: 0.08 h

Procedure:
To 0.48 gm of magnesium in a thoroughly dried flask equipped with condensor and magnetic stirrer was added 2 mls of anhydrous tetrahydrofuran and 0.3 ml of butyl chloride. The mixture was stirred and heated at reflux until reaction initiated (approximately 10 minutes). After 5 minutes, portionwise addition of 3.5 gms of 1,1-diethoxy-9-chloro nonane in 10 ml of tetrahydrofuran was begun. When the addition was complete (15 minutes) the mixture was stirred and heated for 2 hours. It was then cooled to 5° C. in an ice bath and 30 gms of a mixture of 3-chloro-1-pentene (approximately 40%) and 1-chloro-2-pentene (approximately 60%) was added all at once. The mixture was heated slowly and stirred, whereupon it became cloudy. Heating was continued at reflux temperature for 2 hours. The mixture was then cooled, poured into 100 ml of 3 N-hydrochloric acid and diluted with 100 ml of tetrahydrofuran and 150 ml of acetone. The resulting solution was stirred and heated for 30 minutes. It was then concentrated on rotary evaporator and extracted twice with 100 mls of hexane. The organic layer was dried over sodium sulphate, evaporated and distilled. The majority distilled at 110° C. at 0.35 torr and yielded 2.11 gms of 11-tetradecenal.
Reaction SMILES: [CH3:1][Si:2]([CH3:17])([CH3:16])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[CH:9]=[CH:8]1.[Li]CCCC.[CH2:23]([Sn:27](Cl)([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:28][CH2:29][CH2:30][CH3:31])[CH2:24][CH2:25][CH3:26].[Cl-].[NH4+]>C1COCC1.C1CCCCC1>[CH3:1][Si:2]([CH3:17])([CH3:16])[CH2:3][CH2:4][O:5][CH2:6][N:7]1[C:11]2=[N:12][CH:13]=[CH:14][CH:15]=[C:10]2[CH:9]=[C:8]1[Sn:27]([CH2:28][CH2:29][CH2:30][CH3:31])([CH2:32][CH2:33][CH2:34][CH3:35])[CH2:23][CH2:24][CH2:25][CH3:26]
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: C[Si](C)(C)CCOCn1ccc2cccnc21
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: C1CCCCC1
Product: CCCC[Sn](CCCC)(CCCC)c1cc2cccnc2n1COCC[Si](C)(C)C
Temperature: -20 °C
Reaction time: 0.17 h
Yield: 64.7 %

Procedure:
To a solution of 1-(2-trimethylsilylethoxymethyl)-1H-pyrrolo[2,3-b]pyridine (500 mg, 0.0020129 mol) in THF (5 mL) at −10° C. was added a 2.0 M of n-BuLi in cyclohexane (1.2 mL). After 10 min at −10° C., the mixture was cooled to −20° C. and tributyltin chloride (0.65 mL, 0.0024 mol) was added. The mixture was stirred at rt for 1 h, the poured into a 5% aqueous ammonium chloride (20 mL), extracted with EtOAc (3×20 mL) and the combined extracts dried over anhydrous MgSO4 and concentrated in vacuo. The material thus obtained was chromatographed over silica gel eluting with 1:9 EtOAc:hexane to afford 0.7 g of the title compound. 1H NMR (400 MHz DMSO-d6) δ 0.01 (s, 9H), 0.10 (s, 2H), 0.92-0.94 (m, 9H), 1.14-1.27 (m, 6H), 1.37-1.46 (m, 6H), 1.60-1.72 (m, 6H), 3.48-3.52 (m, 2H), 5.71 (s, 2H), 6.74 (s, 1H), 7.16-7.19 (m, 1H), 8.02 (dd, J=1.6, 7.6 Hz, 1H) and 8.31 (dd, J=1.6, 4.4 Hz, 1H).
Reaction SMILES: [CH3:1][C:2]1[O:6][C:5]([NH:7][CH2:8][CH2:9][CH3:10])=[N:4][N:3]=1.[CH:11]1([C:15](Cl)=[O:16])[CH2:14][CH2:13][CH2:12]1.C(N(CC)CC)C>C1C=CC=CC=1>[CH3:1][C:2]1[O:6][C:5]([N:7]([CH2:8][CH2:9][CH3:10])[C:15]([CH:11]2[CH2:14][CH2:13][CH2:12]2)=[O:16])=[N:4][N:3]=1
Reactant: CCCNc1nnc(C)o1
Reactant: O=C(Cl)C1CCC1
Solvent: CCN(CC)CC
Solvent: c1ccccc1
Product: CCCN(C(=O)C1CCC1)c1nnc(C)o1

Procedure:
5-Methyl-2-n-propylamino 1,3,4-oxadiazole (6 g, 0.04 mol) prepared as in (b) above, was refluxed with cyclobutanecarboxylic acid chloride (5.5 g, 0.05 mol) in benzene (25 ml) in the presence of triethylamine (4.72 g, 0.05 mol) for 2 hours. The mixture was filtered and the filtrate washed with dilute HCl, saturated solution NaCHO3 and water; dried over magnesium sulphate, filtered, solvent evaporated off to yield a reddish brown liquid which was distilled twice in a vigreux flask to yield the title compound as a slightly pink liquid (b.p. 110°-111° C./0.27 mm Hg).
Reaction SMILES: [Li][CH2:2]CCC.[Si:6]([O:13][CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([F:24])[CH:18]=1)=O)([C:9]([CH3:12])([CH3:11])[CH3:10])([CH3:8])[CH3:7]>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C1COCC1>[C:9]([Si:6]([O:13][CH2:14][C:15]([C:17]1[CH:22]=[CH:21][C:20]([Cl:23])=[C:19]([F:24])[CH:18]=1)=[CH2:2])([CH3:8])[CH3:7])([CH3:12])([CH3:11])[CH3:10]
Reactant: CC(C)(C)[Si](C)(C)OCC(=O)c1ccc(Cl)c(F)c1
Reactant: [Li]CCCC
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: C1CCOC1
Product: C=C(CO[Si](C)(C)C(C)(C)C)c1ccc(Cl)c(F)c1
Reaction time: 0.5 h
Yield: 40 %

Procedure:
n-BuLi (2.5N, 8.0 mL) was added at −78° C. to a mixture of methyltriphenylphosphonium bromide (5.6 g, 0.15 mol) in THF (50 mL). After being stirred for 0.5 hours, 2-(tert-butyldimethylsilyloxy)-1-(4-chloro-3-fluorophenyl)ethanone (3.9 g, 0.013 mol) was added to the reaction mixture. The mixture was then stirred for 2 hours at 25° C. After quenching with saturated NH4Cl (100 mL), the reaction mixture was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried and concentrated. The residue was purified by silica gel column chromatography eluting with petroleum ether to give tert-butyl (2-(4-chloro-3-fluorophenyl)allyloxy)dimethylsilane (1.6 g, 40% yield).
Reaction SMILES: O[CH2:2][N:3]1[CH2:7][CH:6]([CH2:8][CH2:9][CH3:10])[CH2:5][C:4]1=[O:11].[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([CH:19]=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)[N:21]=2)[CH:18]=1>S(=O)(=O)(O)O.C(O)(=O)C.[Na]>[Cl:12][C:13]1[CH:14]=[CH:15][C:16]2[N:17]([C:19]([CH2:2][N:3]3[CH2:7][CH:6]([CH2:8][CH2:9][CH3:10])[CH2:5][C:4]3=[O:11])=[C:20]([C:22]3[CH:27]=[CH:26][C:25]([CH3:28])=[CH:24][CH:23]=3)[N:21]=2)[CH:18]=1
Reactant: Cc1ccc(-c2cn3cc(Cl)ccc3n2)cc1
Reactant: CCCC1CC(=O)N(CO)C1
Agent: O=S(=O)(O)O
Agent: [Na]
Solvent: CC(=O)O
Product: CCCC1CC(=O)N(Cc2c(-c3ccc(C)cc3)nc3ccc(Cl)cn23)C1

Procedure:
To a refluxing solution of acetic acid (8 ml) and sulfuric acid (2 drops) is added, dropwised, a solution of 1-(hydroxymethyl)-4-propylpyrrolidin-2-one x2 (400 mg, 2.54 mmol) in 3 ml of acetic acid. 6-chloro-2-(4-methylphenyl)imidazo[1,2-a]pyridine x267 (309 mg, 1.27 mmol, 0.5 eq) is then added in once. The reaction mixture is refluxed for 3 days. After cooling, the reaction mixture is slowly poored in 150 ml of concentrated sodium hydroxyde solution (40% wt) and the crude product is extracted by dichloromethane (4×150 ml). The cumulated organic layers are dried over MgSO4, filtered and condensed under reduced pressure leading to the crude product which is purified by flash chromatography over silicagel (hexane/ethyl acetate 80/20). 1-{[6-chloro-2-(4-methylphenyl)imidazo[1,2-a]pyridin-3-yl]methyl}-4-propylpyrrolidin-2-one 4 is recrystallized in ethyl acetate.
Reaction SMILES: BrBr.[Br:3][C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:19])[CH2:11][CH2:12][CH:13]2[O:18][CH2:17][CH2:16][CH2:15][O:14]2)=[CH:6][CH:5]=1.[C:20]([N:27]1[CH2:34][CH2:33][CH2:32][C@H:28]1[C:29]([OH:31])=[O:30])([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21].CCN(C(C)C)C(C)C>C(OCC)C.O1CCOCC1>[N:27]1([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:34][CH2:33][CH2:32][CH:28]1[C:29]([O:31][CH:11]([CH2:12][CH:13]1[O:14][CH2:15][CH2:16][CH2:17][O:18]1)[C:10]([C:7]1[CH:8]=[CH:9][C:4]([Br:3])=[CH:5][CH:6]=1)=[O:19])=[O:30]
Reactant: O=C(CCC1OCCCO1)c1ccc(Br)cc1
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1C(=O)O
Agent: BrBr
Solvent: C1COCCO1
Solvent: CCOCC
Solvent: CCN(C(C)C)C(C)C
Product: CC(C)(C)OC(=O)N1CCCC1C(=O)OC(CC1OCCCO1)C(=O)c1ccc(Br)cc1
Temperature: 24 °C
Reaction time: 0.5 h
Yield: 98.7 %

Procedure:
Bromine (1.3 mL, 25.2 mmol) was added to a solution of Example J2, 1-(4-bromophenyl)-3-(1,3-dioxan-2-yl)propan-1-one (7.7 g, 25.7 mmol) in diethyl ether (60 mL) and 1,4-dioxane (40 mL) and the solution stirred 30 min at 24° C. (Until TLC indicated reaction complete). The solvent was removed by rotory evaporation and the residue was taken up in acetonitrile (350 mL). (S)—N-Boc-Proline (5.54 g, 25.7 mmol) was added followed by dropwise addition of Hunig's base (8.5 mL, 51.5 mmol) and the reaction was stirred 6 hours before being concentrated. The crude product was taken up in CH2Cl2 and charged to a 40 (M) Biotage silica gel cartridge. Gradient elution 15-100% B over 1 L (A=hexanes; B=ethyl acetate) gave Example J3, 2-(1-(4-bromophenyl)-3-(1,3-dioxan-2-yl)-1-oxopropan-2-yl) 1-tert-butyl pyrrolidine-1,2-dicarboxylate 13 g (100%).). RT=2 2 minutes (condition 1); LCMS: Anal. C23H30BrNO7 Calcd. 534; found: 534 (M+Na)+.
Reaction SMILES: CCN(C(C)C)C(C)C.[Cl:10][C:11]1[S:15][C:14]([C:16]2[NH:20][N:19]=[C:18]([C:21]([OH:23])=O)[CH:17]=2)=[CH:13][CH:12]=1.C(C1SC(Cl)=CC=1)(=O)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[NH2:56][CH2:57][C:58]([N:60]1[CH2:65][CH2:64][CH:63]([O:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([C:73]([F:76])([F:75])[F:74])[CH:68]=2)[CH2:62][CH2:61]1)=[O:59]>CN(C=O)C.O>[O:59]=[C:58]([N:60]1[CH2:61][CH2:62][CH:63]([O:66][C:67]2[CH:72]=[CH:71][CH:70]=[C:69]([C:73]([F:76])([F:74])[F:75])[CH:68]=2)[CH2:64][CH2:65]1)[CH2:57][NH:56][C:21]([C:18]1[CH:17]=[C:16]([C:14]2[S:15][C:11]([Cl:10])=[CH:12][CH:13]=2)[NH:20][N:19]=1)=[O:23]
Reactant: O=C(O)c1cc(-c2ccc(Cl)s2)[nH]n1
Reactant: NCC(=O)N1CCC(Oc2cccc(C(F)(F)F)c2)CC1
Agent: CC(=O)c1ccc(Cl)s1
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Solvent: O
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: O=C(NCC(=O)N1CCC(Oc2cccc(C(F)(F)F)c2)CC1)c1cc(-c2ccc(Cl)s2)[nH]n1
Reaction time: 8 h
Yield: 64.7 %

Procedure:
DIPEA (200 mg, 1.5 mmol) was added to a stirred solution of 5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid (100 mg, 0.44 mmol) (prepared by the method used for the synthesis of Intermediate 29, starting from 2-acetyl-5-chlorothiophene) in DMF (2 mL) followed by HOBt (63 mg, 0.46 mmol) and EDCI.HCl (90 mg, 0.46 mmol). After 5 minutes 2-amino-1-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethanone hydrochloride (140 mg, 0.44 mmol) (prepared according to Step 1 and 5 of the General Scheme) was added to the reaction mixture and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with cold water, extracted with ethyl acetate, dried over sodium sulfate and concentrated under reduced pressure. Purification by recrystallisation from 10% EtOAc in hexane afforded 146 mg (65.1% Yield) of 5-(5-chloro-thiophen-2-yl)-1H-pyrazole-3-carboxylic acid {2-oxo-2-[4-(3-trifluoromethyl-phenoxy)-piperidin-1-yl]-ethyl}-amide. LC/MS [M+H]+: 513, 98.3%. 1H NMR (300 MHz, DMSO-d6): δ 13.7 (s, 1H), 8.64 (m, 1H), 7.5 (t, 1H), 7.3 (m, 3H), 7.2 (m, 2H), 6.9 (m, 1H), 4.7 (m, 1H), 4.2 (m, 2H), 3.9 (m, 1H), 3.7 (m, 1H), 3.4 (m, 1H), 3.3 (m, 1H), 1.9 (m, 2H), 1.6 (m, 2H).
Reaction SMILES: [Br:1]Br.[CH2:3]([N:5]1[C:9]([C:10]2[CH:15]=[CH:14][N:13]=[C:12]([NH:16][C:17]3[CH:22]=[CH:21][C:20]([S:23](=[O:30])(=[O:29])[NH:24][CH2:25][CH2:26][O:27][CH3:28])=[CH:19][CH:18]=3)[N:11]=2)=[CH:8][N:7]=[C:6]1[CH3:31])[CH3:4]>C(O)(=O)C>[Br:1][C:15]1[C:10]([C:9]2[N:5]([CH2:3][CH3:4])[C:6]([CH3:31])=[N:7][CH:8]=2)=[N:11][C:12]([NH:16][C:17]2[CH:18]=[CH:19][C:20]([S:23](=[O:30])(=[O:29])[NH:24][CH2:25][CH2:26][O:27][CH3:28])=[CH:21][CH:22]=2)=[N:13][CH:14]=1
Reactant: BrBr
Reactant: CCn1c(-c2ccnc(Nc3ccc(S(=O)(=O)NCCOC)cc3)n2)cnc1C
Solvent: CC(=O)O
Product: CCn1c(-c2nc(Nc3ccc(S(=O)(=O)NCCOC)cc3)ncc2Br)cnc1C
Temperature: 60 °C
Yield: 57.5 %

Procedure:
Bromine (8 μl, 0.14 mmol) was added to a solution of 4-(1-ethyl-2-methylimidazol-5-yl)-2-{4-[N-(2-methoxyethyl)sulphamoyl]anilino}pyrimidine (Method 71; 52 mg, 0.13 mmol) in glacial acetic acid (2 ml) heated at 60° C. The mixture was heated at 60° C. for 4 hours, then the solvent was removed by evaporated. The residue was dissolved in DCM (20 ml), washed with saturated aqueous sodium hydrogen carbonate solution (20 ml), dried (Chemelut column 1005) and purified by flash chromatography eluting with DCM/2% methanolic ammonia (100:0 increasing in polarity to 97:3) to yield the title compound (37 mg, 60%) as a white foam NMR 1.25 (t, 3H), 2.50 (s, 3H), 3.15 (q, 2H), 3.26 (s, 3H), 3.42 (t, 2H), 4.33 (q, 2H), 4.92 (t, 1H), 7.40 (s, 1H), 7.71 (d, 2H), 7.82 (m, 3H), 8.61 (s, 1H); m/z 497.
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6](=[O:32])[NH:7][C:8]2[CH:31]=[CH:30][C:11]([C:12]([N:14]3[CH2:19][CH2:18][N:17]([CH2:20][C:21]4[S:25][C:24]([C:26]([O:28]C)=[O:27])=[CH:23][CH:22]=4)[CH2:16][CH2:15]3)=[O:13])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1.[OH-].[Na+]>CO>[CH:1]1([CH2:4][NH:5][C:6](=[O:32])[NH:7][C:8]2[CH:9]=[CH:10][C:11]([C:12]([N:14]3[CH2:15][CH2:16][N:17]([CH2:20][C:21]4[S:25][C:24]([C:26]([OH:28])=[O:27])=[CH:23][CH:22]=4)[CH2:18][CH2:19]3)=[O:13])=[CH:30][CH:31]=2)[CH2:2][CH2:3]1
Reactant: COC(=O)c1ccc(CN2CCN(C(=O)c3ccc(NC(=O)NCC4CC4)cc3)CC2)s1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(NCC1CC1)Nc1ccc(C(=O)N2CCN(Cc3ccc(C(=O)O)s3)CC2)cc1
Yield: 58.5 %

Procedure:
Methyl 5-((4-(4-(3-(cyclopropylmethyl)ureido)benzoyl)piperazin-1-yl)methyl)-thiophene-2-carboxylate (3.86 mmol, 1.764 g) and sodium hydroxide (3.86 mmol, 0.155 g) were combined and heated to reflux in methanol for 18 hours. The reaction mixture was concentrated at reduced pressure and the resulting residue purified by SCX column chromatography to afford the title compound (1.00 g).
Reaction SMILES: Cl.[CH3:2][C:3]1[NH:8][C:7]2[CH:9]=[N:10][CH:11]=[CH:12][C:6]=2[NH:5][N:4]=1.[C:13]([Cl:24])(=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]>>[ClH:24].[C:13]([N:5]1[C:6]2[CH:12]=[CH:11][N:10]=[CH:9][C:7]=2[NH:8][C:3]([CH3:2])=[N:4]1)(=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: CC1=NNc2ccncc2N1
Reactant: CCCCCCCCCC(=O)Cl
Agent: Cl
Product: CCCCCCCCCC(=O)N1N=C(C)Nc2cnccc21
Yield: 62.7 %

Procedure:
3.7 g (0.02 moles) of 3-methyl-1,4-dihydropyrido[3,4-e]-as-triazine hydrochloride are reacted with an excess of caprinic acid chloride as described in Example 2, to obtain 1-caprinoyl-3-methyl-1,4-dihydropyrido[3,4-e]-as-triazine hydrochloride with a yield of 62.7%; m.p.: 237°-238° C.
Reaction SMILES: [CH2:1]([C:8]1[C:9](=[O:20])[O:10][C:11]2[C:16]([C:17]=1[CH3:18])=[CH:15][CH:14]=[C:13]([OH:19])[CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[I-].[CH3:22][N:23]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[C:24](N1C=C[N+](C)=C1)=[O:25]>>[CH2:1]([C:8]1[C:9](=[O:20])[O:10][C:11]2[C:16]([C:17]=1[CH3:18])=[CH:15][CH:14]=[C:13]([O:19][C:24](=[O:25])[N:23]([CH3:22])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)[CH:12]=2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CN(C(=O)n1cc[n+](C)c1)c1ccccc1
Reactant: Cc1c(Cc2ccccc2)c(=O)oc2cc(O)ccc12
Agent: [I-]
Product: Cc1c(Cc2ccccc2)c(=O)oc2cc(OC(=O)N(C)c3ccccc3)ccc12

Procedure:
The title compound was prepared from 3-benzyl-7-hydroxy-4-methyl-2H-chromen-2-one and 3-(methyl-phenyl-carbamoyl)-1-methyl-3H-imidazol-1-ium iodide. HPLC-MS m/z=400 (M+1), Rt: 4.90 min.
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([N+:21]([O-])=O)=[C:6]([CH:20]=1)[O:7][CH2:8][CH2:9][C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1>C1COCC1.[Ni]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([NH2:21])=[C:6]([O:7][CH2:8][CH2:9][C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[CH:20]=1
Reactant: O=[N+]([O-])c1ccc(F)cc1OCCc1cccc2ccccc12
Agent: [Ni]
Solvent: C1CCOC1
Product: Nc1ccc(F)cc1OCCc1cccc2ccccc12
Yield: 94.4 %

Procedure:
A solution of 1-[2-(5-fluoro-2-nitro-phenoxy)-ethyl]-naphthalene (24.63 g, 79.10 mmol) in THF (200 mL) was shaken with Raney nickel (3.0 g) under H2 (55 psi) for 2 h using Parr apparatus. The reaction mixture was filtered through celite and concentrated. 4-Fluoro-2-(2-naphthalen-1-yl-ethoxy)-phenylamine (21.0 g, 94%) was obtained as a light-yellow solid. 1H NMR (CDCl3, 400 MHz) 8.12 (d, 1H), 7.84 (d, 1H), 7.77 (d, 1H), 7.57-7.42 (m, 4H), 6.60-6.45 (m, 3H), 4.31 (t, 2H), 3.59 (t, 2H).
Reaction SMILES: F[C:2](F)(F)[C:3]([O:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8])=O.[Cl:14][C:15]1[CH:36]=[C:35]([C:37]([F:40])([F:39])[F:38])[CH:34]=[CH:33][C:16]=1[O:17][C:18]1[CH:19]=[CH:20][C:21]([N+:30]([O-:32])=[O:31])=[C:22]([CH:29]=1)[C:23]([O:25]CCO)=[O:24]>CCOCC>[Cl:14][C:15]1[CH:36]=[C:35]([C:37]([F:38])([F:39])[F:40])[CH:34]=[CH:33][C:16]=1[O:17][C:18]1[CH:19]=[CH:20][C:21]([N+:30]([O-:32])=[O:31])=[C:22]([CH:29]=1)[C:23]([O:25][CH2:2][CH2:3][O:5][C:6](=[O:11])[C:7]([F:10])([F:9])[F:8])=[O:24]
Reactant: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Reactant: O=C(OCCO)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Solvent: CCOCC
Product: O=C(OCCOC(=O)C(F)(F)F)c1cc(Oc2ccc(C(F)(F)F)cc2Cl)ccc1[N+](=O)[O-]
Reaction time: 8 h
Yield: 42.2 %

Procedure:
Trifluoroacetic anhydride (8.4 g, 0.04 mole) was added portionwise to a solution of 2-hydroxyethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate (7 g, 0.017 mole) and 50 ml of ether. After holding at 30°-35° C. for an hour, the solution was allowed to stand at room temperature overnight. Excess trifluoroacetic anhydride was removed and 300 ml of ether was added. The ethereal solution was washed three times with water, dried over CaSO4 and concentrated to an oil. Kugelrohr distillation afforded 3.6 g of pure 2-(trifluoroacetoxy)ethyl 5-(2-chloro-4-trifluoromethylphenoxy)-2-nitrobenzoate as a gumming material (yield: 42.2%); nmr (CDCl3) δ 4.62 (s, 4H), 7.02-8.19 (m, 6H); ir (CHCl3) 1752, 1803 Cm-1.
Reaction SMILES: ClC1C=CC(CCC(C2C=CC(OC)=CC=2)=O)=CC=1.[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28]/[C:29](/[C:36]2[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=2)=[CH:30]/[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:23][CH:22]=1>>[Cl:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28]/[C:29](/[C:36]2[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=2)=[CH:30]\[C:31]([O:33][CH2:34][CH3:35])=[O:32])=[CH:23][CH:22]=1
Reactant: CCOC(=O)/C=C(/CCc1ccc(Cl)cc1)c1ccc(OC)cc1
Agent: COc1ccc(C(=O)CCc2ccc(Cl)cc2)cc1
Product: CCOC(=O)/C=C(\CCc1ccc(Cl)cc1)c1ccc(OC)cc1

Procedure:
By a procedure similar to that of example 1.85.3, starting from 3-(4-chlorophenyl)-1-(4-methoxyphenyl)-propan-1-one, (Z)-ethyl 5-(4-chlorophenyl)-3-(4-methoxyphenyl)pent-2-enoate and (E)-ethyl 5-(4-chlorophenyl)-3-(4-methoxyphenyl)pent-2-enoate were obtained as colourless oils.
Reaction SMILES: CS(O[CH:6]([C:15]1[CH:16]=[N:17][C:18]([NH:21][C:22]([C:24]2([C:27]3[CH:35]=[CH:34][C:30]4[O:31][CH2:32][O:33][C:29]=4[CH:28]=3)[CH2:26][CH2:25]2)=[O:23])=[CH:19][CH:20]=1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[O:13][CH3:14])(=O)=O.[N:36]1([CH2:42][CH2:43][OH:44])[CH2:41][CH2:40][NH:39][CH2:38][CH2:37]1.O1C2C=CC(C3(C(NC4C=CC(C(N(C)C)C5C=CC=CC=5OC)=CN=4)=O)CC3)=CC=2OC1>>[O:31]1[C:30]2[CH:34]=[CH:35][C:27]([C:24]3([C:22]([NH:21][C:18]4[CH:19]=[CH:20][C:15]([CH:6]([N:39]5[CH2:40][CH2:41][N:36]([CH2:42][CH2:43][OH:44])[CH2:37][CH2:38]5)[C:7]5[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=5[O:13][CH3:14])=[CH:16][N:17]=4)=[O:23])[CH2:25][CH2:26]3)=[CH:28][C:29]=2[O:33][CH2:32]1
Reactant: OCCN1CCNCC1
Reactant: COc1ccccc1C(OS(C)(=O)=O)c1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)nc1
Agent: COc1ccccc1C(c1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)nc1)N(C)C
Product: COc1ccccc1C(c1ccc(NC(=O)C2(c3ccc4c(c3)OCO4)CC2)nc1)N1CCN(CCO)CC1

Procedure:
1-(Benzo[d][1,3]dioxol-5-yl)-N-(5-((4-(2-hydroxyethyl)piperazin-1-yl)(2-methoxyphenyl)methyl)pyridin-2-yl)cyclopropanecarboxamide was prepared from (6-(1-(benzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamido)pyridin-3-yl)(2-methoxyphenyl)methyl methanesulfonate and 2-(piperazin-1-yl)ethanol in a manner analogous to that of 1-(benzo[d][1,3]dioxol-5-yl)-N-(5-((dimethylamino)(2-methoxyphenyl)methyl)pyridin-2-yl)cyclopropanecarboxamide.
Reaction SMILES: [C:1]([CH2:3][C:4]([O:6]CC)=O)#[N:2].[CH2:9]([NH2:15])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]>COCCO>[CH2:9]([NH:15][C:4](=[O:6])[CH2:3][C:1]#[N:2])[CH2:10][CH2:11][CH2:12][CH2:13][CH3:14]
Reactant: CCCCCCN
Reactant: CCOC(=O)CC#N
Solvent: COCCO
Product: CCCCCCNC(=O)CC#N
Reaction time: 1.5 h

Procedure:
Ethyl cyanoacetate (113 g., 1.0 mole), n-hexylamine (101 g., 1.0 mole) and methyl cellosolve (200 ml.) are refluxed with stirring for 1.5 hours and the solvent is removed under reduced pressure to give N-(n-hexyl) cyanoacetamide.
Reaction SMILES: [Cl:1][C:2]1[N:3]([C@@H:16]2[O:30][C@H:29]([CH2:31][O:32]C(C3C=CC(C)=CC=3)=O)[C@@H:18]([O:19]C(C3C=CC(C)=CC=3)=O)[CH2:17]2)[C:4]2[C:9]([C:10]=1[C:11](=[O:13])[CH3:12])=[CH:8][C:7]([Cl:14])=[C:6]([Cl:15])[CH:5]=2.C[O-].[Na+]>CO>[Cl:1][C:2]1[N:3]([C@@H:16]2[O:30][C@H:29]([CH2:31][OH:32])[C@@H:18]([OH:19])[CH2:17]2)[C:4]2[C:9]([C:10]=1[C:11](=[O:13])[CH3:12])=[CH:8][C:7]([Cl:14])=[C:6]([Cl:15])[CH:5]=2
Reactant: CC(=O)c1c(Cl)n([C@H]2C[C@H](OC(=O)c3ccc(C)cc3)[C@@H](COC(=O)c3ccc(C)cc3)O2)c2cc(Cl)c(Cl)cc12
Agent: C[O-]
Agent: [Na+]
Solvent: CO
Product: CC(=O)c1c(Cl)n([C@H]2C[C@H](O)[C@@H](CO)O2)c2cc(Cl)c(Cl)cc12
Temperature: 25 °C
Reaction time: 16 h
Yield: 73.9 %

Procedure:
2,5,6-Trichloro-3-acetyl-1-[3,5-di-O-(p-toluoyl)-2-deoxy-β-D-ribofuranosyl]indole (4.116, 0.62 g, 1.0 mmol) was suspended in dry MeOH (50 mL) to which was added sodium methoxide (220 mg, 4.1 mmol). The suspension was stirred at room temperature for 16 h, after which time the solution first clarified and a precipitate then formed. The suspension was allowed to stand at 4° C. for 4 h, and was then filtered, and the solids rinsed with cold MeOH (10 mL). The solid was recrystallized from warm MeOH to yield 0.28 g (74%) of 4.117 as a white crystalline solid: mp dec. >200 C; Rf 0.4 (10% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 8.52 (s, 1H), 8.37 (s, 1H), 6.49 (dd, 1H), 5.43 (s, 1H, D2O exch.), 5.26 (s, 1H, D2O exch.), 4.45 (m, 1H), 3.89 (d, 1H), 3.72 (m, 2H), 2.60 (s, 3H), 2.49 (m, 1H), 2.13 (m, 1H). 13C-NMR (125 MHz, DMSO-d6): δ 192.13, 132.15, 131.99, 126.12, 125.50, 125.65, 121.96, 115.25, 112.85, 87.55, 85.43, 69.81, 60.67, 47.10, 30.68. HRMS (EI) m/z calcd. for C15H14Cl3NO4 376.9988, found 376.9982. Anal calcd for C15H14Cl3NO4: C, 47.58; H, 3.73; N, 3.70. Found: C, 47.52; H, 3.95; N, 3.59.