Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[C:12]([CH3:16])([CH3:15])[C:13]#[CH:14])(=O)C.CCN(CC)CC>C1COCC1.Cl[Cu]>[CH3:15][C:12]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([CH3:16])[C:13]#[CH:14]
Reactant: C#CC(C)(C)OC(C)=O
Reactant: Nc1ccccc1
Agent: Cl[Cu]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: C#CC(C)(C)Nc1ccccc1
Yield: 65.9 %

Procedure:
A solution of aniline (19 mL, 0.20 mol), 3-acetoxy-3-methyl-1-butyne (26 g, 0.20 mol), CuCl (1.0 g, 10 mmol) and Et3N (28 mL, 0.20 mol) in THF (120 mL) was heated at reflux for 5 h and was filtered through a pad of Celite™. Removal of solvent and chromatography of the crude mixture (silica gel, EtOAc/hexane, 3/7) afforded 21 g (67%) of 3-methyl-3-phenylamino-1-butyne. Treatment of the aminobutyne with CuCl (0.70 mg, 7.0 mmol) in THF (200 mL) at 70° C. for 16 h followed by chromatography (silica gel, EtOAc/hexane, 3/7) afforded 13 g (60%) of 1,2-dihydro-2,2-dimethylquinoline (structure 75A of Scheme LII, where R1 =H, R2-3 =methyl). Treatment of the quinoline with di-tert-butyl dicarbonate (22 g, 0.10 mol) and DMAP (12 g, 0.10 mol) in THF (100 mL ) for 16 h followed by chromatography (silica gel, EtOAc/hexane, 2/8) afforded 15 g (71%) of 1-tert-butoxycarbonyl-1,2-dihydro-2,2-dimethylquinoline. 1-tert-Butoxycarbonyl-1,2-dihydro-2,2-dimethylquinoline (3.0 g, 11 mmol) in THF (30 mL) was treated with 1.0M BH3 -THF in THF (29 mL, 29 mmol) at rt for 3 h and was quenched with 3M KOH (20 mL). To the above solution 30% H2O2 (5 mL) was added and the mixture was stirred for 60 min, then 5 mL of water was introduced. The mixture was extracted, washed with brine and concentrated. Chromatography of the crude mixture on a silica gel column using a 10-30% mixture of EtOAc/Hexane as eluents afforded a 2:1 mixture of two isomers (0.87 g, 3.1 mmol), which was oxidized with PCC (2.5 g, 11 mmol) in 60 mL of methylene chloride at rt for 60 min. Removal of solvent and chromatography of the black oil on a silica gel column using a 20% mixture of EtOAc and hexane as solvent afforded 0.58 g (68%) of 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2-dimethyl-4-quinolinone as a white solid. Data for 1-tert-butoxycarbonyl-1,2,3,4-tetrahydro-2,2-dimethyl-4-quinolinone: 1H NMR (400 MHz, CDCl3) 7.93 (d, J=7.8, 1H), 7.42 (t, J=7.8, 1H), 7.31 (d, J=7.8, 1H), 7.02 (t, J=7.8, 1H), 2.73 (s, 2H), 1.56 (s, 9H), 1.49 (s, 6H).
Reaction SMILES: [Si]([O:8][C@@H:9]([C@@H:11]1[C@@H:14]([C@H:15]([C:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[S:18])[CH3:16])[N:13]([CH2:26][C:27]([O:29]C(C)(C)C)=[O:28])[C:12]1=[O:34])[CH3:10])(C(C)(C)C)(C)C.B(F)(F)F>C(Cl)Cl>[OH:8][C@@H:9]([C@@H:11]1[C@@H:14]([C@H:15]([C:17]([C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[S:18])[CH3:16])[N:13]([CH2:26][C:27]([OH:29])=[O:28])[C:12]1=[O:34])[CH3:10]
Reactant: C[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1C(=O)N(CC(=O)OC(C)(C)C)[C@@H]1[C@@H](C)C(=S)c1ccc(Cl)cc1
Agent: FB(F)F
Solvent: ClCCl
Product: C[C@@H](O)[C@H]1C(=O)N(CC(=O)O)[C@@H]1[C@@H](C)C(=S)c1ccc(Cl)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of (3S,4S)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-4-[(1R)-1-p-chlorophenylthiocarbonylethyl]-1-(t-butyloxycarbonylmethyl)azetidin-2-one (200 mg) in dry methylene chloride (1.5 ml), there was added BF3 --ET2O complex (263 mg), followed by stirring at room temperature for 1 hour. After evaporation of the solvent, the residue was dissolved in methanol (0.5 ml), diluted with brine and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate and evaporated to give (3S,4S)-3-[(1R)-1-hydroxyethyl]-4-[(1R)-1-p-chlorophenylthiocarbonylethyl]-1-(carboxymethyl)azetidin-2-one as a crude product. The crude product, t-butyldimethylsilyl chloride (246 mg) and imidazole (151 mg) were dissolved in dry dimethylformamide (2.5 ml) and allowed to stand at room temperature overnight. The reaction mixture was poured into cold brine, adjusted with 1M potassium hydrogensulfate to pH and extracted with diethyl ether three times. The organic layer was washed with brine two times, dried over sodium sulfate and evaporated. The residue was purified by silica gel chromatography to give (3S,4S)-3-[(1R)-1-t-butyldimethylsilyloxyethyl]-4-[(1R)-1-p-chlorophenylthiocarbonylethyl]-1-(carboxymethyl)azetidin-2-one.
Reaction SMILES: Br.[CH3:2][N:3]([CH3:25])[CH2:4][CH2:5][CH2:6][C:7]1([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[C:11]2[CH:12]=[CH:13][C:14]([C:16]#[N:17])=[CH:15][C:10]=2[CH2:9][O:8]1.[NH:26]1[CH2:30][CH2:29][CH2:28][CH2:27]1>>[CH3:25][N:3]([CH3:2])[CH2:4][CH2:5][CH2:6][C:7]1([C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[C:11]2[CH:12]=[CH:13][C:14]([C:16]([N:26]3[CH2:30][CH2:29][CH2:28][CH2:27]3)=[NH:17])=[CH:15][C:10]=2[CH2:9][O:8]1
Reactant: CN(C)CCCC1(c2ccc(F)cc2)OCc2cc(C#N)ccc21
Reactant: C1CCNC1
Agent: Br
Product: CN(C)CCCC1(c2ccc(F)cc2)OCc2cc(C(=N)N3CCCC3)ccc21
Temperature: 80 °C
Yield: 40 %

Procedure:
Using 100 mg of 1-[3-(dimethylamino)propyl]-1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran-5-carbonitrile hydrobromide (citalopram HBr) and pyrrolidine (1.2 equiv) gave, after heating at 80° C. for 14 h, title product (58 mg, 40% yield) as a light yellow solid.
Reaction SMILES: Cl.CN(C)CCCN=C=NCC.[CH:13]1([C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([S:27]([C:30]3[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][CH:31]=3)(=[O:29])=[O:28])[CH:19]=2)[CH2:17][CH2:16][CH2:15][CH2:14]1.[CH2:39]([NH2:45])[C@@H:40]1[O:44][CH2:43][CH2:42][CH2:41]1>CN(C)C1C=CN=CC=1.C(Cl)Cl>[CH:13]1([C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([S:27]([C:30]3[CH:31]=[CH:32][C:33]([C:34]([NH:45][CH2:39][C@H:40]4[CH2:41][CH2:42][CH2:43][O:44]4)=[O:35])=[CH:37][CH:38]=3)(=[O:28])=[O:29])[CH:19]=2)[CH2:14][CH2:15][CH2:16][CH2:17]1
Reactant: NC[C@H]1CCCO1
Reactant: O=C(O)c1ccc(S(=O)(=O)n2cc(C3CCCC3)c3ccccc32)cc1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Agent: Cl
Solvent: ClCCl
Product: O=C(NC[C@H]1CCCO1)c1ccc(S(=O)(=O)n2cc(C3CCCC3)c3ccccc32)cc1
Reaction time: 16 h
Yield: 15.6 %

Procedure:
Add 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC; 98 mg, 0.51 mmol, 1.5 equiv) and 4-(dimethylamino)pyridine (DMAP; 70 mg, 0.57 mmol, 1.7 equiv) to a solution of 4-(3-cyclopentylindole-1-sulfonyl)benzoic acid (126 mg, 0.341 mmol, 1 equiv) and (R)-(−)-tetrahydrofurfurylamine (Aldrich; 140 μL, 140 mg, 1.4 mmol, 4.0 equiv) in anhydr CH2Cl2 (1 mL). After stirring 16 h, transfer the reaction solution to a column of silica gel (80 mm×20 mm dia.) and elute (10-45% EtOAc/hex) to give 24 mg (16%) of 4-(3-cyclopentylindole-1-sulfonyl)-N—[(R)-1-(tetrahydrofuran-2-yl)methyl]benzamide as a white foam. MS (m/e): 452.96 (M+1); 451.14 (M−1).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)[S:5][C:6]=1[C@H:7](O)[CH3:8].S(Cl)([Cl:22])=O>ClCCl>[Cl:22][CH:7]([C:6]1[S:5][C:4]([C:10]2[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=2)=[N:3][C:2]=1[CH3:1])[CH3:8]
Reactant: O=S(Cl)Cl
Reactant: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1[C@@H](C)O
Solvent: ClCCl
Product: Cc1nc(-c2ccc(C(F)(F)F)cc2)sc1C(C)Cl
Reaction time: 0.5 h

Procedure:
To a solution of [rac]-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethanol (200 mg, 0.7 mmol; PCT Int. Appl. (2002), WO 02/062774 A1) in dichloromethane (2 ml) was added thionyl chloride (0.1 ml, 1.4 mmol) at −10° C. The cooling bath was removed after 10 min and stirring was continued for 30 min. The solvent was removed under reduced pressure and the residue dried under vacuo to give 220 mg (0.7 mmol, quant.) of the title compound as yellow solid which was used in the next step without further purification.
Reaction SMILES: [O:1]=[C:2]1[NH:6][CH2:5][C@H:4]([C:7]([OH:9])=O)[O:3]1.[N+]([O-])(O)=O.[N+:14]([O:17][CH2:18][CH2:19][NH2:20])([O-:16])=[O:15].C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=O)C=CC=CC=1>>[N+:14]([O:17][CH2:18][CH2:19][NH:20][C:7]([C@@H:4]1[O:3][C:2](=[O:1])[NH:6][CH2:5]1)=[O:9])([O-:16])=[O:15]
Reactant: NCCO[N+](=O)[O-]
Reactant: O=C1NC[C@H](C(=O)O)O1
Agent: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Solvent: O=[N+]([O-])O
Product: O=C1NC[C@H](C(=O)NCCO[N+](=O)[O-])O1
Yield: 20.6 %

Procedure:
Following a procedure similar to that described in Example 1, but using 0.32 g of (5R)-2-oxooxazolidine-5-carboxylic acid, 0.50 g of N-(2-nitrooxyethyl)amine nitrate and 0.63 ml of diphenylphosphoryl azide, 0.11 g of the title compound was obtained as pale yellow plates, melting at 103°-105° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7](=[O:18])[C:6](=[O:19])[NH:5]2.[N+:20]([O-])([O-:22])=[O:21].[K+]>S(=O)(=O)(O)O>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[N+:20]([O-:22])=[O:21])[N:8]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:7](=[O:18])[C:6](=[O:19])[NH:5]2
Reactant: CCOC(=O)Cn1c(=O)c(=O)[nH]c2cc(Cl)ccc21
Reactant: O=[N+]([O-])[O-]
Agent: O=S(=O)(O)O
Agent: [K+]
Product: CCOC(=O)Cn1c(=O)c(=O)[nH]c2cc(Cl)c([N+](=O)[O-])cc21
Yield: 95 %

Procedure:
69.8 g (0.25 mol) of 6-chloro-1-(ethoxycarbonylmethyl)-2,3(1H,4H)-quinoxalinedione were dissolved in 625 ml of concentrated sulfuric acid and, at 0° C., 25 g (0.25 mol) of potassium nitrate were added a little at a time. The cooling was then removed, and the mixture was stirred until reaction was complete. The mixture was poured into ice-water, and the precipitate was filtered off with suction to yield 77.8 g (95%) of the product.
Reaction SMILES: Br[CH2:2][C:3]1[N:4]([CH3:28])[C:5]2[C:10]([N:11]=1)=[C:9]([N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1)[N:8]=[C:7]([N:18]1[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[N:20]=[C:19]1[CH3:27])[N:6]=2.[F:29][C:30]([F:37])([F:36])[CH:31]1[CH2:35][CH2:34][NH:33][CH2:32]1>>[CH3:28][N:4]1[C:3]([CH2:2][N:33]2[CH2:34][CH2:35][CH:31]([C:30]([F:37])([F:36])[F:29])[CH2:32]2)=[N:11][C:10]2[C:5]1=[N:6][C:7]([N:18]1[C:22]3[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=3[N:20]=[C:19]1[CH3:27])=[N:8][C:9]=2[N:12]1[CH2:17][CH2:16][O:15][CH2:14][CH2:13]1
Reactant: FC(F)(F)C1CCNC1
Reactant: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CBr)n(C)c2n1
Product: Cc1nc2ccccc2n1-c1nc(N2CCOCC2)c2nc(CN3CCC(C(F)(F)F)C3)n(C)c2n1

Procedure:
4-(8-(Bromomethyl)-9-methyl-2-(2-methyl-1H-benzo[d]imidazol-1-yl)-9H-purin-6-yl)morpholine (50 mg) was reacted with 3-(trifluoromethyl)pyrrolidine via General Procedure E to give 19.9 mg of 289 following reverse phase purification. MS (Q1) 501.2 (M)+
Reaction SMILES: Cl.[CH3:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][N:11]=1)[C:6]([OH:8])=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CN1CCOCC1.[CH3:43][O:44][C:45]1[C:46]2[N:59]=[C:58]([NH2:60])[S:57][C:47]=2[C:48]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[N:49][CH:50]=1>C1COCC1>[CH3:43][O:44][C:45]1[C:46]2[N:59]=[C:58]([NH:60][C:6](=[O:8])[C:5]3[CH:9]=[CH:10][N:11]=[C:3]([CH3:2])[CH:4]=3)[S:57][C:47]=2[C:48]([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)=[N:49][CH:50]=1
Reactant: Cc1cc(C(=O)O)ccn1
Reactant: COc1cnc(-c2ccccc2)c2sc(N)nc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: C1CCOC1
Solvent: CN1CCOCC1
Product: COc1cnc(-c2ccccc2)c2sc(NC(=O)c3ccnc(C)c3)nc12

Procedure:
From 2-methyl-isonicotinic acid hydrochloride, HATU and N-methylmorpholine in THF, then treatment with 7-methoxy-4-phenyl-thiazolo[5,4-c]pyridin-2-ylamine. ES-MS m/e (%): 377 (M+H+, 100).
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[C:8]([S:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([C:18]3([O:24][CH3:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH:12]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=O.Cl.[NH2:27][OH:28]>>[Cl:1][C:2]1[CH:9]=[C:8]([S:10][C:11]2[CH:16]=[C:15]([F:17])[CH:14]=[C:13]([C:18]3([O:24][CH3:25])[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[CH:12]=2)[CH:7]=[CH:6][C:3]=1[CH:4]=[N:27][OH:28]
Reactant: COC1(c2cc(F)cc(Sc3ccc(C=O)c(Cl)c3)c2)CCOCC1
Reactant: NO
Agent: Cl
Product: COC1(c2cc(F)cc(Sc3ccc(C=NO)c(Cl)c3)c2)CCOCC1
Yield: 83 %

Procedure:
Using an analogous procedure to that described in Example 68, 2-chloro-4-[5-fluoro-3-(4-methoxytetrahydropyran-4-yl)phenylthio]benzaldehyde was reacted with hydroxylamine hydrochloride to give 2-chloro-4-[5-fluoro-3-(4-methoxytetrahydropyran-4-yl)phenylthio]benzaldehyde oxime in 83% yield as a gum.
Reaction SMILES: [H-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([OH:15])=[C:10]([C:16]1[CH:21]=[CH:20][C:19]([S:22][CH3:23])=[CH:18][CH:17]=1)[CH:9]=[CH:8]2.F[C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1.O>CN(C)C=O>[CH3:3][O:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11]([O:15][C:25]1[CH:30]=[CH:29][C:28]([N+:31]([O-:33])=[O:32])=[CH:27][CH:26]=1)=[C:10]([C:16]1[CH:21]=[CH:20][C:19]([S:22][CH3:23])=[CH:18][CH:17]=1)[CH:9]=[CH:8]2
Reactant: O=[N+]([O-])c1ccc(F)cc1
Reactant: COc1ccc2c(O)c(-c3ccc(SC)cc3)ccc2c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc2c(Oc3ccc([N+](=O)[O-])cc3)c(-c3ccc(SC)cc3)ccc2c1
Temperature: 60 °C
Reaction time: 0.5 h

Procedure:
Place sodium hydride (1.05 eq.) in dry dimethylformamide in a 3 neck flask equipped with a mechanical stirrer, addition funnel with nitrogen purge, and a temperature probe under nitrogen. Charge the addition funnel with 6-methoxy-2-(4-methylthiophenyl)naphthalene-1-ol (1 eq.) dissolved in dry dimethylformamide. Add this solution dropwise to the stirred sodium hydride solution at a rate that holds the temperature below 35° C. Stir the reaction mixture for 30 minutes before adding 4-fluoronitrobenzene with additional dry dimethylformamide. Heat the solution to 60° C. Once the reaction is complete, cool the flask and add water slowly to cause precipitation of the product. Filter the crude product and wash with water and then methyl tert-butyl ether. Dry the filter cake in a vacuum oven to give 6-methoxy-2-(4-methylthiophenyl)-1-(4-nitrophenoxy)naphthalene.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.[CH2:8]([NH2:11])[CH2:9][NH2:10]>N1C=CC=CC=1>[NH2:10][CH2:9][CH2:8][NH:11][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1
Reactant: Brc1ccccn1
Reactant: NCCN
Solvent: c1ccncc1
Product: NCCNc1ccccn1

Procedure:
2-Bromopyridine (15.8 g), ethylene diamine (30 g) and pyridine (10 ml) were heated together under reflux for 3 hr. The mixture was stripped to remove the excess of ethylene diamine and the residue taken up in water. The pH was adjusted to 14 and extracted with chloroform. The extracts were dried (K2CO3), stripped and the residue distilled at reduced pressure to give 2-(2-aminoethylamino) pyridine, 8.24 g (60%) bp 80° C., 0.01 mm Hg. (ii) A mixture of sodium hydride (0.53 g) and 2-(aminoethylamino)pyridine (2.74 g) in DMSO (30 ml) was heated slowly to 85° C. under nitrogen. After the evolution of hydrogen had ceased the solution was cooled to room temperature and benzyl bromide (2.37 ml) added dropwise keeping the temperature below 30° C. After a further 1 hr, water (200 ml) was added, the mixture extracted with ether and the extract washed with 2N hydrochloric acid. The pH of the aqueous layer was adjusted to 4.5 and extracted with chloroform. The pH was further raised to 14 and extracted with ether. After drying (K2CO3) and stripping, the final ether extract gave 2-[N-(2-aminoethyl)-N-benzylamino]pyridine (2.58 g) as an oil which was used without further purification.
Reaction SMILES: Cl[C:2](Cl)(Cl)[C:3](=N)[O:4][C@H:5]1[O:22][C@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:6]1[O:7][C:8](=[O:10])[CH3:9].OC1C=[CH:38][C:35]([CH:36]=[O:37])=[CH:34][CH:33]=1.B(F)(F)F.CCOCC.C([O-])(O)=O.[Na+]>C(Cl)Cl>[C:8]([O:7][C@@H:6]1[C@@H:11]([O:12][C:13](=[O:15])[CH3:14])[C@H:16]([O:17][C:18](=[O:20])[CH3:19])[C@@H:21]([CH2:23][O:24][C:25](=[O:27])[CH3:26])[O:22][CH:5]1[O:4][C:3]1[CH:33]=[CH:34][C:35]([CH:36]=[O:37])=[CH:38][CH:2]=1)(=[O:10])[CH3:9]
Reactant: O=Cc1ccc(O)cc1
Reactant: CC(=O)OC[C@H]1O[C@H](OC(=N)C(Cl)(Cl)Cl)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@H]1OC(C)=O
Agent: FB(F)F
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: CCOCC
Product: CC(=O)OC[C@H]1OC(Oc2ccc(C=O)cc2)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Temperature: -20 °C
Reaction time: 4 h
Yield: 42 %

Procedure:
2,3,4,6-Tetra-O-acetyl-α-D-galactopyranosyl 2,2,2-trichloroacetimidate 1 (9.85 g, 20 mmol) and 4-hydroxybenzaldehyde (3.66 g, 30 mmol) were dissolved in CH2Cl2 (100 mL) and then the reaction mixture was cooled to −20° C. Boron trifluoride diethyl etherate (46%, 16 mL, 60 mmol) was added dropwise at this temperature. The reaction mixture was stirred at −20° C. for 4 h and was monitored by TLC. Saturated NaHCO3 aqueous solution (150 mL) was added to the mixture. The aqueous layer was separated and extracted with CH2Cl2 (2×150 mL). The organic layers were combined, dried over MgSO4 and concentrated. Purification by silica gel column chromatography yielded 2 (3.8 g, 42%) as a white solid.
Reaction SMILES: O[C:2]1([CH3:14])[C:11]2[C:6](=[C:7]([CH3:13])[CH:8]=[C:9]([CH3:12])[CH:10]=2)[CH2:5][CH2:4][CH2:3]1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[CH3:14][C:2]1[C:11]2[C:6](=[C:7]([CH3:13])[CH:8]=[C:9]([CH3:12])[CH:10]=2)[CH2:5][CH2:4][CH:3]=1
Reactant: Cc1cc(C)c2c(c1)C(C)(O)CCC2
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CC1=CCCc2c(C)cc(C)cc21
Yield: 85 %

Procedure:
Following the procedure of Example 1, step 2, 26.64 g (0.140 mol) of 1-hydroxy-1,5,7-trimethyl-1,2,3,4-tetrahydronaphthalene in 300 ml of toluene was reacted with 0.30 g of p-toluenesulphonic acid monohydrate. Vacuum distillation yielded 20.49 g (85%) of the title product as a pale yellow liquid, b.p. 67°-70° C./0.12 mm of Hg. NMR δ(CDCl3) 2.04 (3H, m), 2.21-2.25 (2H, m), 2.25 (3H, s), 2.30 (3H, s), 2.66 (2H, t, J=8.1 Hz), 5.83 (1H, m), 6.87 (1H, s), 6.94 (1H, s).
Reaction SMILES: [C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6](=O)[CH2:5]1)(=[O:3])[CH3:2].C1(P(=[CH:35][C:36]([O:38][CH3:39])=[O:37])(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[C:10]([O:13][CH3:14])[CH:11]=2)[C:6]([CH2:35][C:36]([O:38][CH3:39])=[O:37])=[CH:5]1)(=[O:3])[CH3:2]
Reactant: COc1ccc2c(c1)N(C(C)=O)CC2=O
Reactant: COC(=O)C=P(c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: COC(=O)Cc1cn(C(C)=O)c2cc(OC)ccc12
Yield: 50 %

Procedure:
A mixture of 1-acetyl-6-methoxy-1,2-dihydro-3H-indol-3-one (3.96 g, 19.3 mmol) (Example 12) and methyl (triphenylphosphoranylidene)acetate (19.75 g, 57.9 mmol) in toluene (60 mL) was heated at reflux under argon for 24 h. The mixture was loaded on silica gel and eluted with EtOAc/hexane (1/5) to yield a thick oil (2.52 g, 50%). LC/MS m/z 262 (M+H)+; 1H NMR (400 MHz, CDCl3) δ 8.04 (br s, 1H), 7.38 (d, 1H), 7.31 (s, 1H), 6.92 (dd, 1H), 3.89 (s, 3H), 3.74 (s, 3H), 3.71 (d, 2H), 2.62 (s, 3H).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH:14]1[CH2:16][CH2:15]1)[C:6]([CH2:17]Cl)=[C:5]2[O:19][CH2:20][CH2:21][CH2:22][CH3:23].[C:24]1(=[O:34])[NH:28][C:27](=[O:29])[C:26]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:25]12.[K].O>CN(C)C=O>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][CH:14]1[CH2:16][CH2:15]1)[C:6]([CH2:17][N:28]1[C:24](=[O:34])[C:25]3[C:26](=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:27]1=[O:29])=[C:5]2[O:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCOc1c(CCl)n(CC2CC2)c(=O)c2ccc(Br)cc12
Reactant: O=C1NC(=O)c2ccccc21
Agent: [K]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCOc1c(CN2C(=O)c3ccccc3C2=O)n(CC2CC2)c(=O)c2ccc(Br)cc12
Yield: 92.1 %

Procedure:
A solution of 6-bromo-4-butoxy-3-chloromethyl-2-cyclopropylmethyl-1(2H)-isoquinolinone (5.58 g, 14 mmol) and potassium phthalimide (3.89 g, 21 mmol) in N,N-dimethylformamide (50 mL) was stirred at room temperature for 5 h. The reaction mixture was poured into water and extracted with ethyl acetate. After washing the extract with water, the extract was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained crystals were recrystallized from tetrahydrofuran-n-hexane to give 2-[(6-bromo-4-butoxy-2-cyclopropylmethyl-1-oxo-1,2-dihydro-3-isoquinolinyl)methyl]-1H-isoindole-1,3(2H)-dione (6.57 g, 94.7%) as crystals.
Reaction SMILES: Cl[C:2]1[N:3]=[CH:4][C:5]2[C:11](=[O:12])[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:18][CH3:19])[C:6]=2[N:7]=1.[CH2:20]([N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)[CH3:21]>C(Cl)(Cl)Cl>[CH2:20]([N:22]1[CH2:27][CH2:26][N:25]([C:2]2[N:3]=[CH:4][C:5]3[C:11](=[O:12])[C:10]([C:13]([O:15][CH2:16][CH3:17])=[O:14])=[CH:9][N:8]([CH2:18][CH3:19])[C:6]=3[N:7]=2)[CH2:24][CH2:23]1)[CH3:21]
Reactant: CCN1CCNCC1
Reactant: CCOC(=O)c1cn(CC)c2nc(Cl)ncc2c1=O
Solvent: ClC(Cl)Cl
Product: CCOC(=O)c1cn(CC)c2nc(N3CCN(CC)CC3)ncc2c1=O
Yield: 90.7 %

Procedure:
3.8 g of 2-chloro-5-oxo-6-carbethoxy-8-ethyl-5,8-dihydro-pyrido(2,3-d)pyrimidine and 2.9 g of 1-ethylpiperazine, dissolved in 50 cm3 of chloroform, are heated under reflux for 2 hours. After cooling, the organic solution is washed with water and dried over MgSO4 ; the solvent is evaporated and the residue is recrystallised from a mixture of isopropyl ether (15 cm3) and benzene (25 cm3) and gives 4.4 g (yield: 93%) of 2-(4'-ethylpiperazino)-5-oxo-8-ethyl-6-carbethoxy-5,8-dihydro-pyrido(2,3-d)pyrimidine; melting point 161° C.
Reaction SMILES: [OH:1][C:2]1[CH:16]=[CH:15][C:5]([C:6]([N:8]([CH:12]([CH3:14])[CH3:13])[CH:9]([CH3:11])[CH3:10])=[O:7])=[CH:4][C:3]=1[O:17][CH3:18].[H-].[Na+].[C:21]([C:23]1[CH:34]=[CH:33][C:26]([O:27][CH2:28][CH2:29][CH2:30][CH2:31]Cl)=[CH:25][CH:24]=1)#[N:22]>CN(C)C=O>[C:21]([C:23]1[CH:34]=[CH:33][C:26]([O:27][CH2:28][CH2:29][CH2:30][CH2:31][O:1][C:2]2[CH:16]=[CH:15][C:5]([C:6]([N:8]([CH:9]([CH3:11])[CH3:10])[CH:12]([CH3:13])[CH3:14])=[O:7])=[CH:4][C:3]=2[O:17][CH3:18])=[CH:25][CH:24]=1)#[N:22]
Reactant: N#Cc1ccc(OCCCCCl)cc1
Reactant: COc1cc(C(=O)N(C(C)C)C(C)C)ccc1O
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1cc(C(=O)N(C(C)C)C(C)C)ccc1OCCCCOc1ccc(C#N)cc1
Temperature: 0 °C
Reaction time: 0.17 h

Procedure:
A stirred solution of 4-hydroxy-3-methoxy-N,N-bis(1-methylethyl)benzamide (1.0 g, 4.0 mmol) in 50 mL of N,N-dimethylformamide is treated with 60% sodium hydride (160 mg, 4.0 mmol). After stirring at 0° C. for 10 minutes, the reaction is treated with 4-(4-cyanophenoxy)butyl chloride (835 mg, 4.0 mmol) and stirred at 60° C. for 4 days. The reaction is partitioned between diethyl ether and water. The organic layer is washed with brine, dried over magnesium sulfate, and concentrated in vacuo. The resulting material is purified by chromatography on silica gel (30 g) with 60 % ethyl acetate/hexane as the eluent to afford 4-[4-(4-cyanophenoxy)butoxy]-3-methoxy-N,N-bis(1-methylethyl)benzamide as an oil.
Reaction SMILES: [C:1]1([N:7]2[CH:11]=[C:10]([Si](C)(C)C)[NH:9][N:8]2C(N)=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CC1C=CC(S(Cl)(=O)=O)=CC=1.O.[N:31]1C=CC=C[CH:32]=1>>[C:1]1([N:7]2[C:11]([C:32]#[N:31])=[CH:10][NH:9][NH:8]2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: c1ccncc1
Reactant: C[Si](C)(C)C1=CN(c2ccccc2)N(C(N)=O)N1
Agent: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: O
Product: N#CC1=CNNN1c1ccccc1
Temperature: 130 °C
Reaction time: 24 h

Procedure:
3-phenyl-5-trimethylsilanyl-1H-[1,2,3]triazole-2-carboxylic acid amide (550 mg) which is the compound prepared in the above 3) was dissolved in 2.0 ml of pyridine, 801 mg of 4-methylbenzenesulfonic acid chloride was added thereto and the mixture was stirred at 130° C. for one day. Water was added to the reaction solution, the mixture was extracted with ethyl acetate and the ethyl acetate layer washed with a saturated saline solution and dried over sodium sulfate. After the solvent was evaporated in vacuo and the residue was separated and purified by a thin-layer chromatography (hexane/ethyl acetate=5/1) to give 113 mg of the title compound as a white solid.