Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([C:17]([O:19][C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1)=[O:18])[C@H:3]1[CH2:8][CH2:7][C@H:6]([CH2:9][CH2:10]COS(C)(=O)=O)[CH2:5][CH2:4]1.[CH2:30]([NH:32][CH2:33][CH2:34][OH:35])[CH3:31].[Na+].[I-].[CH3:38]C(N(C)C)=O>>[F:27][C:26]([F:28])([F:29])[C:23]1[CH:24]=[CH:25][C:20]([O:19][C:17](=[O:18])[N:2]([C@H:3]2[CH2:8][CH2:7][C@H:6]([CH2:9][CH2:10][CH2:38][N:32]([CH2:30][CH3:31])[CH2:33][CH2:34][OH:35])[CH2:5][CH2:4]2)[CH3:1])=[CH:21][CH:22]=1
Reactant: CCNCCO
Reactant: CN(C(=O)Oc1ccc(C(F)(F)F)cc1)[C@H]1CC[C@H](CCCOS(C)(=O)=O)CC1
Reactant: CC(=O)N(C)C
Agent: [I-]
Agent: [Na+]
Product: CCN(CCO)CCC[C@H]1CC[C@H](N(C)C(=O)Oc2ccc(C(F)(F)F)cc2)CC1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 293 mg (corresponds to 0.5 mmol) of trans-Methanesulfonic acid 3-{4-[methyl-(4-trifluoromethyl-phenoxycarbonyl)-amino]-cyclohexyl}-propyl ester in 2.5 ml of DMA was cooled to 0° C., treated with 0.195 ml (2 mmol) of Ethyl-(2-hydroxy-ethyl)-amine and stirred over night at RT. A catalytic amount of NaI and 0.195 ml (2 mmol) of Ethyl-(2-hydroxy-ethyl)-amine and after 9 h, 0.88 ml (1 mmol) of Ethyl-(2-hydroxy-ethyl)-amine were added. After 16 h, the solvent was evaporated and the residue extracted with aqueous saturated NaHCO3/Et2O (3×). The organic phase was dried with Na2SO4, filtered and evaporated. Purification by flash column chromatography on silica gel (CH2Cl2/MeOH 9:1) gave 48 mg (22%) of pure trans-(4-{3-[Ethyl-(2-hydroxy-ethyl)-amino]-propyl}-cyclohexyl)-methyl-carbamic acid 4-trifluoromethyl-phenyl ester, MS: 431 (MH+). The following compounds were prepared in analogy:
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH3:11])[N:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[S:19]([N:22]=[C:23]=[O:24])(=[O:21])=[O:20]>C(#N)C>[Cl:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=1[S:19]([NH:22][C:23]([NH:1][C:2]1[N:7]=[C:6]([O:8][CH3:9])[N:5]=[C:4]([NH:10][CH3:11])[N:3]=1)=[O:24])(=[O:21])=[O:20]
Reactant: CNc1nc(N)nc(OC)n1
Reactant: O=C=NS(=O)(=O)c1ccccc1Cl
Solvent: CC#N
Product: CNc1nc(NC(=O)NS(=O)(=O)c2ccccc2Cl)nc(OC)n1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To a solution of 2.1 g of 2-amino-4-methoxy-6-methylamino-1,3,5-triazine in 60 ml of hot acetonitrile was added, dropwise, 3.3 g of 2-chlorobenzenesulfonylisocyanate in 20 ml of acetonitrile. After stirring for 18 hours at room temperature, the mixture was filtered to yield the product named above melting at 224°-228°.
Reaction SMILES: [CH:1]([C@@H:4]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH2:18][CH2:19][CH2:20][O:21][CH3:22])[CH:10]=1)[C:5](O)=[O:6])([CH3:3])[CH3:2].[BH4-].[Na+].II.CO>O1CCCC1>[CH:1]([C@@H:4]([CH2:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[C:11]([O:17][CH2:18][CH2:19][CH2:20][O:21][CH3:22])[CH:10]=1)[CH2:5][OH:6])([CH3:3])[CH3:2]
Reactant: COCCCOc1cc(C[C@@H](C(=O)O)C(C)C)ccc1OC
Agent: II
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Product: COCCCOc1cc(C[C@@H](CO)C(C)C)ccc1OC
Reaction time: 96 h

Procedure:
186 g of 2(R)-isopropyl-3-[4-methoxy-3-(3-methoxypropyloxy)-phenyl]-propionic acid in 0.5 liter of tetrahydrofuran are added dropwise at room temperature to a stirred mixture of 27.2 g of sodium borohydride in 1.5 liters of tetrahydrofuran. After 45 minutes a solution of 76.2 g of iodine in 1 liter of tetrahydrofuran is added dropwise. The reaction mixture is stirred for 4 days and then 1 liter of methanol is carefully added dropwise. After evaporation of the solvent the residue is taken up in 2 liters of 2N hydrochloric acid and extracted repeatedly with ethyl acetate. The organic extracts are washed in succession with water, saturated sodium thiosulfate solution, water/saturated sodium chloride solution (1:1), 0.1N sodium hydroxide solution and saturated sodium chloride solution. The organic extracts are concentrated by evaporation and purified by FC (2.4 kg of silica gel, ethyl acetate/hexane=1:4). The title compound is obtained: Rf (ethyl acetate/hexane=1:1)=0.28.
Reaction SMILES: C[O:2][C:3](=O)[C:4]1[CH:9]=[C:8]([NH2:10])[CH:7]=[CH:6][C:5]=1[O:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[NH2:19][NH2:20]>>[NH2:10][C:8]1[CH:7]=[CH:6][C:5]([O:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[C:4]([CH:9]=1)[C:3]([NH:19][NH2:20])=[O:2]
Reactant: NN
Reactant: COC(=O)c1cc(N)ccc1Oc1ccccc1
Product: NNC(=O)c1cc(N)ccc1Oc1ccccc1
Yield: 76 %

Procedure:
A mixture of phenol (5.64 g, 60 mmol) and potassium t-butoxide (6.74 g, 60 mmol) in 50 mL 1,4-dioxane was stirred at room temperature for 0.5 h. To the mixture was added 2-chloro-5-nitro-benzoic acid methyl ester (10.78 g, 50 mmol) and the mixture was refluxed overnight. The solvent was evaporated and the residue was purified by chromatography with EtOAc:hexanes, 1:4, as eluant, yielding (11.739 g, 86%) 5-nitro-2-phenoxy-benzoic acid methyl ester. A mixture of 5-nitro-2-phenoxy-benzoic acid methyl ester (2.0 g, 7.32 mmol) in 30 mL ethanol and Pd/C (200 mg) were hydrogenated at 40 psi overnight to yield 5-amino-2-phenoxy-benzoic acid methyl ester (1.672 g, 94%). A mixture of 5-amino-2-phenoxy-benzoic acid methyl ester (0.95 g, 3.9 mmol) and hydrazine (4 mL, 80%) was refluxed for 4 h to yield 5-amino-2-phenoxy-benzoic acid hydrazide (0.722 g, 76%). The title compound was prepared from 5-amino-2-phenoxy-benzoic acid hydrazide and 3-trifluoromethyl-benzaldehyde by a procedure similar to Example 22. 1H NMR (CDCl3): 10.81 (s, 1H), 8.15 (s, 1H), 8.0 (s, 1H), 7.98 (d, J=7.5 Hz, 1H), 7.66 (s, 1H), 7.64 (d, J=7.5 Hz, 1H), 7.53 (t, J=7.2 Hz, 1H), 7.40 (m, 2H), 7.19 (t, J=7.5 Hz, 1H), 7.07 (d, J=7.8, 2H), 6.80 (m, 2H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([O:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:5]([NH:8][C:9]([NH2:11])=[S:10])=[N:6][CH:7]=1.Br[CH2:20][C:21]([CH:23]1[CH2:28][CH2:27][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:25][CH2:24]1)=O>>[Br:1][C:2]1[CH:3]=[C:4]([O:12][C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:5]([NH:8][C:9]2[S:10][CH:20]=[C:21]([CH:23]3[CH2:24][CH2:25][N:26]([C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])[CH2:27][CH2:28]3)[N:11]=2)=[N:6][CH:7]=1
Reactant: NC(=S)Nc1ncc(Br)cc1Oc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CCC(C(=O)CBr)CC1
Product: CC(C)(C)OC(=O)N1CCC(c2csc(Nc3ncc(Br)cc3Oc3ccccc3)n2)CC1

Procedure:
Following the procedure in Example 7, step E using 1-(5-bromo-3-phenoxypyridin-2-yl)thiourea and tert-butyl 4-(2-bromoacetyl)piperidine-1-carboxylate provided tert-butyl 4-(2-(5-bromo-3-phenoxypyridin-2-ylamino)thiazol-4-yl)piperidine-1-carboxylate.
Reaction SMILES: [C:1]1([C:7]2[O:11][C:10]([C:12]3[C:13]([NH2:20])=[N:14][CH:15]=[C:16]([CH:18]=[CH2:19])[N:17]=3)=[N:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N+](=[CH:23][C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N-]>C1(C)C=CC=CC=1>[NH2:20][C:13]1[N:14]=[CH:15][C:16]([CH:18]2[CH2:19][CH:23]2[C:24]([O:26][CH2:27][CH3:28])=[O:25])=[N:17][C:12]=1[C:10]1[O:11][C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[N:8][N:9]=1
Reactant: CCOC(=O)C=[N+]=[N-]
Reactant: C=Cc1cnc(N)c(-c2nnc(-c3ccccc3)o2)n1
Solvent: Cc1ccccc1
Product: CCOC(=O)C1CC1c1cnc(N)c(-c2nnc(-c3ccccc3)o2)n1
Temperature: 110 °C

Procedure:
To a vial charged with 3-(5-phenyl-1,3,4-oxadiazol-2-yl)-5-vinyl-pyrazin-2-amine (26 mg, 0.01 mmol) under an atmosphere of nitrogen at room temperature was slowly added a solution of ethyl 2-diazoacetate (34 mg, 31 μL, 0.1 mmol) in toluene (350 μL) over a period of 10 min. The reaction mixture was heated at 110° C. for 1 h. The reaction mixture was cooled to room temperature and the solvent was removed under reduced pressure. The crude material was dissolved in DMSO (1 mL), filtered and purified via reverse phase column chromatography using 10 to 99% MeOH—H2O (TFA modifier) to obtain ethyl 2-[5-amino-6-(5-phenyl-1,3,4-oxadiazol-2-yl)pyrazin-2-yl]cyclopropanecarboxylate. 1H NMR (400.0 MHz, CDCl3) δ 8.23-8.15 (m, 3H), 7.59-7.50 (m, 3H), 4.19 (q, J=7.1 Hz, 2H), 2.64 (dd, J=6.2, 12.7 Hz, 1H), 2.25 (dd, J=5.5, 12.4 Hz, 1H), 1.66-1.61 (m, 2H) and 1.39-1.24 (m, 3H) ppm; LC/MS m/z 352.2 [M+H]+.
Reaction SMILES: [C:1]([O:5][C@@H:6]([C:10]1[C:11]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)=[C:12]2[C:17](=[CH:18][C:19]=1[CH3:20])[N:16]=[C:15]([C:21]1N[N:24]=[CH:23][CH:22]=1)[CH:14]=[CH:13]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2].N1C=CC(B(O)O)=[CH:35][CH:34]=1>>[C:1]([O:5][C@@H:6]([C:10]1[C:11]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)=[C:12]2[C:17](=[CH:18][C:19]=1[CH3:20])[N:16]=[C:15]([C:21]1[CH:22]=[CH:23][N:24]=[CH:35][CH:34]=1)[CH:14]=[CH:13]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1cc2nc(-c3ccn[nH]3)ccc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Reactant: OB(O)c1ccncc1
Product: Cc1cc2nc(-c3ccncc3)ccc2c(-c2ccc(Cl)cc2)c1[C@H](OC(C)(C)C)C(=O)O
Reaction time: 3 h

Procedure:
(S)-2-tert-Butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-(pyridin-4-yl)quinolin-6-yl)acetic acid (73) was prepared following the procedure used for (S)-2-tert-butoxy-2-(5-(4-chlorophenyl)-7-methyl-2-(1H-pyrazol-5-yl)quinolin-6-yl)acetic acid of Example 70 except that pyridin-4-ylboronic acid was used instead of 1H-pyrazol-5-ylboronic acid and in the final step the reaction was stirred for 3 hours.
Reaction SMILES: [CH3:1][C:2]1([CH3:39])[C:26]2[CH2:27][CH2:28][N:29]([CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:30][C:25]=2[C:5]2[C:6]([OH:24])=[CH:7][C:8]([CH:10]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:11])=[CH:9][C:4]=2[O:3]1.[ClH:40].[N:41]1([CH2:46][CH2:47][CH2:48][C:49](O)=[O:50])[CH2:45][CH2:44][CH2:43][CH2:42]1.C1(N=C=NC2CCCCC2)CCCCC1>>[ClH:40].[CH3:39][C:2]1([CH3:1])[C:26]2[CH2:27][CH2:28][N:29]([CH2:31][CH2:32][C:33]3[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=3)[CH2:30][C:25]=2[C:5]2[C:6]([O:24][C:49](=[O:50])[CH2:48][CH2:47][CH2:46][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)=[CH:7][C:8]([CH:10]([CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23])[CH3:11])=[CH:9][C:4]=2[O:3]1
Reactant: CCCCCCCCCCCCC(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2CN(CCc2ccccc2)CC1
Reactant: O=C(O)CCCN1CCCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Product: CCCCCCCCCCCCC(C)c1cc(OC(=O)CCCN2CCCC2)c2c(c1)OC(C)(C)C1=C2CN(CCc2ccccc2)CC1

Procedure:
5,5-Dimethyl-10-hydroxy-2-phenethyl-8-(2-tetradecyl)-1,2,3,4-tetrahydro-5H-[ 1]benzopyrano[3,4-d]pyridine, γ-pyrrolidinobutyric acid hydrochloride and dicyclohexylcarbodiimide are reacted in equimolar amounts according to Example 1 to produce the desired product.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([O:17][C@H:18]([C:22]4[CH:27]=[CH:26][C:25]([S:28][CH:29]5[CH2:31][CH2:30]5)=[CH:24][CH:23]=4)[C@@H:19]([NH2:21])[CH3:20])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.CN(C)C(N(C)C)=N.[F:40][C:41]([F:48])([F:47])[C:42](OCC)=[O:43]>CO>[CH:29]1([S:28][C:25]2[CH:24]=[CH:23][C:22]([C@@H:18]([O:17][C:13]3[CH:12]=[C:11]4[C:16](=[CH:15][CH:14]=3)[N:8]([C:5]3[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=3)[N:9]=[CH:10]4)[C@@H:19]([NH:21][C:42](=[O:43])[C:41]([F:48])([F:47])[F:40])[CH3:20])=[CH:27][CH:26]=2)[CH2:31][CH2:30]1
Reactant: C[C@H](N)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccc(SC2CC2)cc1
Reactant: CCOC(=O)C(F)(F)F
Agent: CN(C)C(=N)N(C)C
Solvent: CO
Product: C[C@H](NC(=O)C(F)(F)F)[C@H](Oc1ccc2c(cnn2-c2ccc(F)cc2)c1)c1ccc(SC2CC2)cc1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(1R,2S)-1-{[1-(4-Fluorophenyl)-1H-indazol-5-yl]oxy}-1-[4-(cyclopropylthio)phenyl]propan-2-amine (62 mg, 0.14 mmol) was dissolved in MeOH (2 mL), 1,1,3,3-tetramethylguanidine (100 μL, 0.8 mmol) and ethyl trifluoroacetate (83 μL, 0.7 mmol) was added. The mixture was stirred at r.t. for 2 h, the solvents was removed by evaporation and the residual material was treated with water and a few drops of dilute HCl(aq) until slightly acidic. The formed slurry was extracted with DCM and EtOAc, the combined organic phases was concentrated and purified by semi-preparative HPLC using a Kromasil® C18 250×20 mm, 5 μm column. Flow 10 mL/min, 15 min gradient of 50%-90% MeCN in water followed by isocratic final concentration until product had eluted. UV=254 nm was used for detection. Fractions with product was combined and lyophilized to afford the title compound as a colourless solid. Yield 59 mg (79%).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[C:7]([N+:12]([O-:14])=[O:13])[CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:15][C:16]([F:25])([F:24])[C:17]1[CH:18]=[C:19]([OH:23])[CH:20]=[CH:21][CH:22]=1.C([O-])([O-])=O.[K+].[K+]>CC#N>[N+:12]([C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][CH:3]=[C:2]2[O:23][C:19]1[CH:20]=[CH:21][CH:22]=[C:17]([C:16]([F:15])([F:24])[F:25])[CH:18]=1)([O-:14])=[O:13]
Reactant: Oc1cccc(C(F)(F)F)c1
Reactant: O=[N+]([O-])c1cccc2c(Cl)ccnc12
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Product: O=[N+]([O-])c1cccc2c(Oc3cccc(C(F)(F)F)c3)ccnc12
Temperature: 100 °C
Yield: 37.4 %

Procedure:
A suspension of 4-chloro-8-nitroquinoline (200 mg, 0.96 mmol), 3-(trifluoromethyl)phenol (250 mg, 1.54 mmol), K2CO3 (414 mg, 2.99 mmol) in CH3CN (2 mL) was heated in a sealed tube at 100° C. for 8 h. Then the reaction mixture was quenched with water and was extracted with EtOAc. The organic layer was washed with brine, separated, dried, filtered and concentrated. The residue was purified by column chromatography to afford 120 mg of the title product. 1H NMR (300 MHz, DMSO d6): δ 8.83 (d, J=5.4 Hz, 1H), 8.60-8.57 (d, J=8.4 Hz, 1H), 8.36 (d, J=6.9 Hz, 1H), 7.85-7.73 (m, 5H), 6.87 (d, J=5.4 Hz, 1H).
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:7][S:8]([Cl:11])(=[O:10])=[O:9]>C(Cl)Cl>[Cl-:11].[S:8]([NH+:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1)([CH3:7])(=[O:10])=[O:9]
Reactant: C1CNCCN1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Product: CS(=O)(=O)[NH+]1CCNCC1
Product: [Cl-]
Temperature: 25 °C
Reaction time: 12 h
Yield: 26.5 %

Procedure:
To a stirred solution of piperazine (4.3 g; 50 mmol) in CH2Cl2 (50 ml) at +5 C. was added a solution of CH3SO2Cl (4.25 ml; 55 mmol) in CH2Cl2 (15 ml). The thick reaction mixture was stirred at rt. for 12 h, added CH2Cl2 (100 ml), and extracted with 1 M HCl (300 ml). A precipitate formed in the aqueous phase was filtered of to give 2.66 g of N-mesylpiperazinium chloride (32%).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.[O:12]=[C:13]1[C:18]2=[CH:19][NH:20][C:21]([CH:22]=O)=[C:17]2[CH2:16][CH2:15][O:14]1>>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[C:5]2=[CH:22][C:21]1[NH:20][CH:19]=[C:18]2[C:13](=[O:12])[O:14][CH2:15][CH2:16][C:17]=12
Reactant: O=C1Cc2cc(Br)ccc2N1
Reactant: O=Cc1[nH]cc2c1CCOC2=O
Product: O=C1Nc2ccc(Br)cc2C1=Cc1[nH]cc2c1CCOC2=O

Procedure:
5-Bromo-1,3-dihydro-indol-2-one was condensed with 4-oxo-2,4,6,7-tetrahydro-pyrano[3,4-c]pyrrole-1-carbaldehyde to give the title compound.
Reaction SMILES: [OH:1][N:2]1[C:6](=[O:7])[CH:5]2[CH2:8][CH:9]([CH3:12])[CH2:10][CH2:11][CH:4]2[C:3]1=[O:13].C(N(CC)CC)C.[C:21](Cl)(=[O:24])[CH:22]=[CH2:23]>ClCCCl>[C:21]([O:1][N:2]1[C:6](=[O:7])[CH:5]2[CH2:8][CH:9]([CH3:12])[CH2:10][CH2:11][CH:4]2[C:3]1=[O:13])(=[O:24])[CH:22]=[CH2:23]
Reactant: C=CC(=O)Cl
Reactant: CC1CCC2C(=O)N(O)C(=O)C2C1
Solvent: ClCCCl
Solvent: CCN(CC)CC
Product: C=CC(=O)ON1C(=O)C2CCC(C)CC2C1=O
Temperature: 25 °C
Yield: 90.4 %

Procedure:
Next, 10.07 g (0.055 mol) of N-hydroxy-4-methylhexahydrophthalimide, 15 ml (0.11 mol) of triethylamine, and 50 ml of 1,2-dichloroethane were poured in a 100 ml flask. Then, 7.2 ml (0.090 mol) of acrylyl chloride was slowly dropped therein at a room temperature under nitrogen with stirring. After the dropping, a mixture thus prepared was reacted for one hour at a room temperature. A reaction mixture was washed with water so as to separate an organic layer therefrom. Then, the organic layer was washed with a 5% sodium hydrogen carbonate aqueous solution. The organic layer separated from the 5% sodium hydrogen carbonate aqueous solution was dried with magnesium sulfate, and then a solvent was removed from the organic layer. 11.8 g of N-(acryloyloxy)-4-methylhexahydrophthalimide (viscous liquid of dark yellow color) was thereby obtained. N-(acryloyloxy)-4-methylhexahydrophthalimide is represented by the following formula (120):
Reaction SMILES: C(N(CC)CC)C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.I[C:28]1[C:29](=[O:43])[NH:30][C:31](=[O:42])[N:32]([CH:41]=1)[C@@H:33]1[O:40][C@H:37]([CH2:38][OH:39])[CH2:36][C@H:34]1O.[C:44]([O:50][CH3:51])(=[O:49])[CH:45]=[CH:46][CH:47]=[CH2:48].[O:52]1CCOCC1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:44]([CH:45]=[CH:46][CH:47]=[CH:48][C:28]1[C:29](=[O:43])[NH:30][C:31](=[O:42])[N:32]([CH:41]=1)[C@@H:33]1[O:40][C@H:37]([CH2:38][OH:39])[C@@H:36]([OH:52])[CH2:34]1)([O:50][CH3:51])=[O:49]
Reactant: C=CC=CC(=O)OC
Reactant: O=c1[nH]c(=O)n([C@@H]2O[C@H](CO)C[C@H]2O)cc1I
Reactant: C1COCCO1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: CCN(CC)CC
Product: COC(=O)C=CC=Cc1cn([C@H]2C[C@H](O)[C@@H](CO)O2)c(=O)[nH]c1=O
Temperature: 70 °C

Procedure:
A solution of triethylamine (3.9 mL, 28.2 mmol) in dioxane (12 mL) was deareated by bubbling nitrogen through for 15 min. Palladium acetate (0.60 g, 0.26 mmol) and triphenylphosphine (0.183 g, 0.70 mmol) were added and the solution was heated at 70° C. for 20 min to give a dark brown solution. 5-Iodo-3′-deoxyuridine (5.0 g, 14.1 mmol) and methyl 2,4-pentadienoate (2.5 g, 22.3 mmol) was added and the mixture was heated under reflux for 15 h. The solvent and volatile components were evaporated in vacuo and the residue was partitioned between water (15 mL) and EtOAc (15 mL). The phases were separated and the aqueous phase was extracted twice with EtOAc (10 mL each). The combined organic phase was washed with brine and concentrated. The residue was dissolved in MeOH (15 mL) and allowed to cool to room temperature. The solid formed was collected by filtration, washed with a small quantity of MeOH and dried in vacuo to give 0.38 g brown powder.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]=[N:10][C:11]2[CH:19]=[C:15]([C:16](Cl)=[O:17])[C:14]([OH:20])=[CH:13][CH:12]=2)=[CH:5][CH:4]=1.[C:21]([N:24]1[C:28]2=[CH:29][C:30]([CH3:32])=[N:31][N:27]2[C:26]([C:33]2[CH:38]=[C:37]([NH2:39])[CH:36]=[CH:35][C:34]=2[O:40][CH3:41])=[N:25]1)(=[O:23])[CH3:22]>>[C:21]([N:24]1[C:28]2=[CH:29][C:30]([CH3:32])=[N:31][N:27]2[C:26]([C:33]2[CH:38]=[C:37]([NH:39][C:16](=[O:17])[C:15]3[CH:19]=[C:11]([N:10]=[N:9][C:6]4[CH:7]=[CH:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=4)[CH:12]=[CH:13][C:14]=3[OH:20])[CH:36]=[CH:35][C:34]=2[O:40][CH3:41])=[N:25]1)(=[O:23])[CH3:22]
Reactant: COc1ccc(N)cc1-c1nn(C(C)=O)c2cc(C)nn12
Reactant: COc1ccc(N=Nc2ccc(O)c(C(=O)Cl)c2)cc1
Product: COc1ccc(N=Nc2ccc(O)c(C(=O)Nc3ccc(OC)c(-c4nn(C(C)=O)c5cc(C)nn45)c3)c2)cc1

Procedure:
5-(4-Methoxyphenylazo)salicoyl chloride and 1-acetyl-3-(5-amino-2-methoxyphenyl)-6-methyl-1H-pyrazolo[3,2-c]-s-triazole were reacted together as described for the preparation of Dye 7. The product crystallized as the monohydrate from aqueous pyridine, m.p. 282°-3°, λmax (methanol) = 350 nm.
Reaction SMILES: [Cl:1][CH2:2][CH2:3][CH2:4][CH:5]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=2)[NH:9][CH:8]=1)[OH:6].N1C2C(=CC(C#N)=CC=2)C=C1.ClCCCC(Cl)=O>>[Cl:1][CH2:2][CH2:3][CH2:4][C:5]([C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([C:16]#[N:17])[CH:14]=2)[NH:9][CH:8]=1)=[O:6]
Reactant: N#Cc1ccc2[nH]cc(C(O)CCCCl)c2c1
Agent: N#Cc1ccc2[nH]ccc2c1
Agent: O=C(Cl)CCCCl
Product: N#Cc1ccc2[nH]cc(C(=O)CCCCl)c2c1

Procedure:
In the second reaction line is schematically illustrated the synthesis of the intermediate 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile of Formula (I) through the condensing of indol-5-carbonitrile with 4-chlorobutyrylchloride to give 3-(4-chlorobutyryl)-1H-indol-5-carbonitrile, which is reduced with sodium borohydride, to give 3-(4-chloro-1-hydroxy-butyl)-1H-indol-5-carbonitrile.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:6]=[CH:7][C:8]=1[O:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=2)[N:13]=[CH:12][CH:11]=1)[NH2:5].C(N(CC)CC)C.ClC(Cl)(O[C:35](=[O:41])OC(Cl)(Cl)Cl)Cl.[CH2:43]([N:50]1[CH2:55][CH2:54][CH:53]([NH2:56])[CH2:52][CH2:51]1)[C:44]1[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=1>C(Cl)(Cl)Cl.O>[CH2:43]([N:50]1[CH2:55][CH2:54][CH:53]([NH:56][C:35]([NH:5][C:4]2[CH:6]=[CH:7][C:8]([O:9][C:10]3[C:19]4[C:14](=[CH:15][C:16]([O:22][CH3:23])=[C:17]([O:20][CH3:21])[CH:18]=4)[N:13]=[CH:12][CH:11]=3)=[C:2]([Cl:1])[CH:3]=2)=[O:41])[CH2:52][CH2:51]1)[C:44]1[CH:45]=[CH:46][CH:47]=[CH:48][CH:49]=1
Reactant: NC1CCN(Cc2ccccc2)CC1
Reactant: O=C(OC(Cl)(Cl)Cl)OC(Cl)(Cl)Cl
Reactant: COc1cc2nccc(Oc3ccc(N)cc3Cl)c2cc1OC
Solvent: ClC(Cl)Cl
Solvent: O
Solvent: CCN(CC)CC
Product: COc1cc2nccc(Oc3ccc(NC(=O)NC4CCN(Cc5ccccc5)CC4)cc3Cl)c2cc1OC
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 67.7 %

Procedure:
3-Chloro-4-[(6,7-dimethoxy-4-quinolyl)oxy]aniline (100 mg) was dissolved in chloroform (10 ml) and triethylamine (1 ml) to prepare a solution. A solution of triphosgene (134 mg) in chloroform was then added to the solution, and the mixture was stirred at room temperature for 10 min. Next, 1-benzyl-4-piperidineamine (86 mg) was added thereto, and the mixture was further stirred at room temperature for one hr. Water was added to stop the reaction, and the reaction solution was then extracted with chloroform, followed by concentration. The residue was purified on a column using chloroform/methanol to give the title compound (112 mg, yield 68%).
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][C:5](=[O:14])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].[NH:15]1[CH:19]=[CH:18][N:17]=[CH:16]1.O>CN(C)C=O>[CH2:2]([N:15]1[CH:19]=[CH:18][N:17]=[CH:16]1)[CH2:3][CH2:4][C:5](=[O:14])[CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: c1c[nH]cn1
Reactant: CCCCCCCCC(=O)CCCBr
Solvent: CN(C)C=O
Solvent: O
Product: CCCCCCCCC(=O)CCCn1ccnc1

Procedure:
1-Bromo-4-dodecanone 6.45 and imidazole (8.34 g) in dimethylformamide (10 ml) at 0° C. were stirred overnight at ambient temperature, then one day at 80° C. The resulting mixture was poured into water (200 ml), extracted with ether (3×75 ml) and the extracts were dried (magnesium sulfate) and evaporated. Chromatography of the product on silica gel eluting with 7% methanol in methylene chloride gave 1-(dodecan-4-on-1-yl)imidazole.
Reaction SMILES: [OH:1][CH:2]([C:11]#[C:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8].C(Br)(Br)(Br)Br.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>>[OH:1][C@@H:2]([C:11]#[C:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:3][CH2:4][CH2:5][CH2:6][C:7]([O:9][CH3:10])=[O:8]
Reactant: CCCCCCCCCCCCC#CC(O)CCCCC(=O)OC
Agent: BrC(Br)(Br)Br
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Product: CCCCCCCCCCCCC#C[C@H](O)CCCCC(=O)OC

Procedure:
This compound was prepared by reaction of methyl 6-(±)-hydroxy-7-eicosynoate (preparative example V) with CBr4 /Ph3P reagent in exactly the same manner as described in preparative example VIII. Note: By use of the corresponding 6-R, and 6-S alcohols (preparative example VI) the optically active (+) and (-) 6-bromo-7-eicosynoates were also obtained.