Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:12][C@H:11]2[CH3:24])=[O:9])=[C:4]([O:27][C:28]#[N:29])[CH:3]=1.[N-:30]=[N+:31]=[N-:32].[Na+]>CC(C)=O.O>[Cl:1][C:2]1[CH:26]=[CH:25][C:5]([O:6][CH2:7][C:8]([N:10]2[CH2:15][CH2:14][N:13]([CH2:16][C:17]3[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=3)[CH2:12][C@H:11]2[CH3:24])=[O:9])=[C:4]([O:27][C:28]2[N:30]=[N:31][NH:32][N:29]=2)[CH:3]=1
Reactant: [N-]=[N+]=[N-]
Reactant: C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1OC#N
Agent: [Na+]
Solvent: O
Solvent: CC(C)=O
Product: C[C@@H]1CN(Cc2ccc(F)cc2)CCN1C(=O)COc1ccc(Cl)cc1Oc1nn[nH]n1
Temperature: 25 °C

Procedure:
To a solution of 2-(4-chloro-2-cyanato-phenoxy)-1-[4-(4-fluoro-benzyl)-(2R)-2-methyl-piperazin-1-yl]-ethanone (0.17 g, 0.427 mmol) in acetone (2 mL) was added sodium azide (0.061 g, 0.94 mmol) and the reaction was stirred at reflux for 3 hours, then cooled to ambient temperature and stirred 18 hours. The reaction was diluted with water and extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The product was purified by anion exchange chromatography to give the title compound as its acetic acid addition salt (0.073 g, LRMS: 461.2, 463.3).
Reaction SMILES: [CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:9]=[CH:8][C:7]([C:10](=[O:15])[CH2:11][N:12]=[N+]=[N-])=[CH:6][CH:5]=1.[ClH:17].[H][H]>CO.[Pd]>[ClH:17].[CH3:1][O:2][C:3](=[O:16])[C:4]1[CH:5]=[CH:6][C:7]([C:10](=[O:15])[CH2:11][NH2:12])=[CH:8][CH:9]=1
Reactant: COC(=O)c1ccc(C(=O)CN=[N+]=[N-])cc1
Reactant: [H][H]
Agent: [Pd]
Agent: Cl
Solvent: CO
Product: COC(=O)c1ccc(C(=O)CN)cc1
Yield: 86.7 %

Procedure:
4(2-Azido-acetyl)-benzoic acid methyl ester (6.53 mmol) was suspended in methanol (30 ml) and aqueous hydrochloric acid (6.53 mmol, 1M) was added. A catalytic amount of palladium on carbon (10% wt) was added and the reaction stirred over an atmosphere of hydrogen for 3 h. The reaction was filtered and the solvent removed in vacuo to give the title compound (1.3 g) as a yellow solid m/z=194 in MS ES+, which was used in the next step without purification.
Reaction SMILES: [F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[C:5]([CH:11]=[CH:12][CH:13]=1)[O:6][CH:7]1[CH2:10][NH:9][CH2:8]1.C(N1CC(OC2C=CC=C(C(F)(F)F)C=2)C1)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:44][C:45]1[CH:50]=[CH:49][CH:48]=[C:47]([CH3:51])[C:46]=1[N:52]=[C:53]=[S:54]>C(Cl)Cl>[CH3:51][C:47]1[CH:48]=[CH:49][CH:50]=[C:45]([CH3:44])[C:46]=1[NH:52][C:53]([N:9]1[CH2:10][CH:7]([O:6][C:5]2[CH:11]=[CH:12][CH:13]=[C:3]([C:2]([F:1])([F:14])[F:15])[CH:4]=2)[CH2:8]1)=[S:54]
Reactant: Cc1cccc(C)c1N=C=S
Reactant: FC(F)(F)c1cccc(OC2CNC2)c1
Agent: FC(F)(F)c1cccc(OC2CN(C(c3ccccc3)c3ccccc3)C2)c1
Solvent: ClCCl
Product: Cc1cccc(C)c1NC(=S)N1CC(Oc2cccc(C(F)(F)F)c2)C1

Procedure:
Crude 3-[3-(trifluoromethyl)phenoxy]azetidine from catalytic debenzylation of 30.0 g (0.078 mole) of 1-benzhydryl-3-[3-(trifluoromethyl)phenoxy]azetidine was dissolved in 100 ml of methylene chloride and treated dropwise under a nitrogen atmosphere with a solution of 12.7 g (0.078 mole) of 2,6-dimethylphenylisothiocyanate in 25 ml of methylene chloride. The product began to precipitate during the addition and an additional 50 ml of methylene chloride was added to facilitate stirring. After stirring overnight at ambient temperature, the product was collected by filtration (13.5 g, m.p. 196°-199° C.) A 6.0 g sample was recrystallized from isopropanol to give 5.3 g of product, m.p. 197°-199° C.
Reaction SMILES: FC(F)(F)C(O)=O.[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([NH:15][C:16](=[O:30])[NH:17][C:18]2[S:26][C:21]3[CH2:22][NH:23][CH2:24][CH2:25][C:20]=3[C:19]=2[C:27]([NH2:29])=[O:28])=[CH:11][CH:10]=1.C(N(C(C)C)CC)(C)C.Br[CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43]>O1CCCC1.C(Cl)Cl>[C:27]([C:19]1[C:20]2[CH2:25][CH2:24][N:23]([CH2:41][C:42]([O:44][C:45]([CH3:48])([CH3:47])[CH3:46])=[O:43])[CH2:22][C:21]=2[S:26][C:18]=1[NH:17][C:16]([NH:15][C:12]1[CH:11]=[CH:10][C:9]([Cl:8])=[CH:14][CH:13]=1)=[O:30])(=[O:28])[NH2:29]
Reactant: CC(C)(C)OC(=O)CBr
Reactant: NC(=O)c1c(NC(=O)Nc2ccc(Cl)cc2)sc2c1CCNC2
Solvent: CCN(C(C)C)C(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC(C)(C)OC(=O)CN1CCc2c(sc(NC(=O)Nc3ccc(Cl)cc3)c2C(N)=O)C1
Yield: 63.6 %

Procedure:
A solution of compound A4 (300 mg, 0.646 mmol), diisopropylethylamine (0.350 mL, 1.97 mmol), and tert-butyl 2-bromoacetate (0.140 mL, 0.950 mmol) in tetrahydrofuran (4 mL) was stirred at room temperature for 8 h. After this time, the reaction mixture was diluted with methylene chloride (10 mL), sonicated, and filtered to afford compound E1 as a light yellow solid (191 mg, 64%): 1H NMR (500 MHz, DMSO-d6) δ 10.93 (s, 1H), 10.18 (s, 1H), 7.59-7.29 (m, 5H), 6.89 (bs, 1H), 3.61 (s, 2H), 3.30 (s, 2H), 2.82-2.76 (m, 4H), 1.43 (s, 9H). MS (M+H) 465.
Reaction SMILES: [C:1]1([CH3:15])[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14].I[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.P(C(C)(C)C)(C(C)(C)C)C(C)(C)C.CC(C)([O-])C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:15][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[N:7]([C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[CH3:14]
Reactant: Cc1ccccc1Nc1ccccc1C
Reactant: Ic1ccccc1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Solvent: Cc1ccccc1
Product: Cc1ccccc1N(c1ccccc1)c1ccccc1C
Temperature: 120 °C
Yield: 98 %

Procedure:
A mixture of di-o-tolylamine (Compound 9) (6.00 g, 30.4 mmol), iodobenzene (12.2 g, 60 mmol), Pd(OAc)2 (0.34 g, 1.5 mmol), P(t-Bu)3 (0.6 g, 3 mmol), sodium tert-butoxide (5.76 g, 60 mmol) in toluene (120 mL) was degassed and heated at about 120° C. for 40 hours. The resulting mixture was diluted with ethyl acetate (200 mL), washed with brine, dried over Na2SO4, loaded on silica gel and purified by flash column using eluents of hexanes to give a white solid (Compound 10) (8.2 g, in 98% yield).
Reaction SMILES: [F:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([F:28])[C:3]=1[C:4]([NH:6][C:7]1[S:8][C:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=2)=[C:10]([CH:12]=O)[N:11]=1)=[O:5].[N+](=[C:31](P(=O)(OC)OC)C(=O)C)=[N-].C([O-])([O-])=O.[K+].[K+]>CO.C(Cl)Cl>[C:12]([C:10]1[N:11]=[C:7]([NH:6][C:4](=[O:5])[C:3]2[C:2]([F:1])=[CH:27][CH:26]=[CH:25][C:24]=2[F:28])[S:8][C:9]=1[C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)#[CH:31]
Reactant: O=Cc1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Reactant: COP(=O)(OC)C(=[N+]=[N-])C(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CO
Product: C#Cc1nc(NC(=O)c2c(F)cccc2F)sc1-c1cccc(C(F)(F)F)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 20.4 %

Procedure:
Into a solution of Compound 67 (50.0 mg, 0.12 mmol) and dimethyl 1-diazo-2-oxopropylphosphonate (46.0 mg, 0.24 mmol) in MeOH (1.00 mL) was added K2CO3 (50.0 mg, 0.36 mmol) was added. The mixture was stirred at room temperature overnight, diluted with CH2Cl2, washed with water, dried (Na2SO4), filtered and concentrated. The residue was purified on silica to give Compound 104 (10.0 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:16]=[C:15]([N:17]([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:18][CH2:19][CH2:20][CH2:21][OH:22])[CH:14]=[CH:13][C:10]=1[CH:11]=[O:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N1C=CN=C1.[C:32]([Si:36](Cl)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)([CH3:35])([CH3:34])[CH3:33].O>CN(C)C=O.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([N:17]([CH2:23][CH2:24][CH2:25][CH3:26])[CH2:18][CH2:19][CH2:20][CH2:21][O:22][Si:36]([C:32]([CH3:35])([CH3:34])[CH3:33])([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH:14]=[CH:13][C:10]=1[CH:11]=[O:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Reactant: CCCCN(CCCCO)c1ccc(C=O)c(OCc2ccccc2)c1
Agent: c1c[nH]cn1
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: CCCCN(CCCCO[Si](c1ccccc1)(c1ccccc1)C(C)(C)C)c1ccc(C=O)c(OCc2ccccc2)c1
Temperature: 25 °C
Yield: 76.5 %

Procedure:
In 20 ml of N,N-dimethylformamide were dissolved 1.63 g (4.59 mmol) of 2-benzyloxy-4-[butyl(4-hydroxybutyl)amino]benzaldehyde and 1.2 g (17.63 mmol) of imidazole. To this mixture, 1.27 g (4.62 mmol) of tert-butylchlorodiphenylsilane was added dropwise with stirring at room temperature. The mixture was stirred for 2 hours. After the reaction mixture was poured into water, extraction with ethyl acetate, washing with a saturated saline solution, and drying over anhydrous sodium sulfate were performed. The residue was purified by silica gel column chromatography to give 2.08 g of a colorless oily matter (yield: 76.5%).
Reaction SMILES: N([O-])=O.[Na+].N[C:6]1[C:7]([CH3:15])=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10].S(=O)(=O)(O)[OH:17]>O>[OH:17][C:6]1[C:7]([CH3:15])=[C:8]([CH:12]=[CH:13][CH:14]=1)[C:9]([OH:11])=[O:10]
Reactant: O=S(=O)(O)O
Reactant: Cc1c(N)cccc1C(=O)O
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: Cc1c(O)cccc1C(=O)O
Temperature: -10 °C
Reaction time: 0.5 h

Procedure:
Alternatively, the desired subtitled compound was prepared by adding 22.6 g (0.33 mol) of sodium nitrite in small portions to a cooled (-10° C.) solution of 45 g (0.30 mol) of 3-amino-2-methylbenzoic acid and 106 g (58 mL; 1.08 mol) of concentrated sulfuric acid in 400 mL of water, while maintaining the temperature below 70° C. The resultant reaction mixture was stirred for approximately 30 minutes at -10° C., poured into a solution of 240 mL of concentrated sulfuric acid in 1.2 L water, and then slowly heated to 80° C. (heavy gas evolution occurs between the temperatures of 40°-60° C.). When the gas evolution stopped, the reaction mixture was cooled to room temperature and the subtitled compound was extracted five times with ethyl acetate (600 mL). The combined organic phases were combined with 500 mL of an aqueous saturated sodium carbonate solution. The resultant layers were separated and the aqueous layer was acidified to pH 2 with concentrated hydrochloric acid. The titled compound was then extracted using ethyl acetate (500 mL) and the combined organic phases were washed with brine, dried over sodium sulfate, filtered and then concentrated under reduced pressure to provide a crude material. This material was purified using two recrystallizations from a ethyl acetate/chloroform mixture to provide 23.2 g of a light orange powder.
Reaction SMILES: C[Mg]Cl.[Cl:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]#[CH:16].[CH:17](OCC)([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20].[Cl-].[NH4+]>O1CCCC1.C1(C)C=CC=CC=1.O.C(O)(=O)C>[Cl:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]#[C:16][CH:17]([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20]
Reactant: CCOC(OCC)OCC
Reactant: C#CCCCCCCCCCCCl
Agent: C[Mg]Cl
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CC(=O)O
Solvent: Cc1ccccc1
Product: CCOC(C#CCCCCCCCCCCCl)OCC
Temperature: 47.5 °C
Reaction time: 1 h
Yield: 82 %

Procedure:
In a reactor equipped with a stirrer, a cooling condenser, a dropping funnel and a thermometer was placed a solution of methyl magnesium chloride (89.7 g:1.2 mol) in tetrahydrofuran (370.0 g), and stirred at a solution temperature of from 45 to 50° C. The 12-chloro-1-dodecyne (200.8 g:1.0 mol) was dropwise added thereto at a reaction mixture temperature of from 50 to 60° C. over 1 hour, and then stirred at from 60 to 65° C. for 5 hours. Then, a solution of triethyl orthoformate (177.8 g:1.2 mol) in toluene (120.0 g) was dropwise added at a reaction mixture of from 80 to 85° C. over 30 minutes, and then stirred at from 90 to 95° C. for 6 hours. After completion of the reaction was confirmed by gas chromatography, acetic acid (57.0 g), ammonium chloride (35.0 g) and water (400.0 g) were added to the reaction mixture. The organic phase separated from the aqueous phase was washed with an aqueous 1.0% sodium hydroxide solution (170.0 g). The organic phase was subjected to removal of the solvent under reduced pressure, and then the residue was distilled under reduced pressure to obtain 13-chloro-1,1-diethoxy-2-tridecyne [bp: 156-163° C./0.13 KPa, 249.2 g, 0.82 mol]. [Yield: 82.3%]
Reaction SMILES: [CH:1](=[O:11])/[CH:2]=[CH:3]/[CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[BH4-].[Na+]>CO>[CH2:1]([OH:11])/[CH:2]=[CH:3]/[CH:4]=[CH:5][CH2:6][CH2:7][CH2:8][CH2:9][CH3:10]
Reactant: CCCCCC=C/C=C/C=O
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CCCCCC=C/C=C/CO
Temperature: 0 °C
Yield: 83 %

Procedure:
6.08 g (40 mmols) of trans, trans-2,4-decadienal was dissolved in 50 ml of methanol and 379 mg (10 mmols) of sodium borohydride was added slowly to the solution while stirring and cooling at a temperature of 0° C. After disappearance of the starting material had been confirmed, the mixture was concentrated under reduced pressure. An aqueous solution of ammonium chloride was added to the mixture to decompose the complex compound formed, and the mixture was extracted with diethyl ether. The ethereal layer was washed with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The extract was then filtered and the filtrate was concentrated under reduced pressure. The residue thus obtained was distilled under reduced pressure to obtain 5.08 g (83% yield) of trans, trans-2,4-decadienol as an oily substance having a boiling point of 75°-87° C./0.3 mmHg.
Reaction SMILES: [CH2:1]([N:8]1[C:13](=O)[CH2:12][O:11][C@@H:10]([CH3:15])[C@@H:9]1[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C1COCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][O:11][C@@H:10]([CH3:15])[C@@H:9]1[C:16]([O:18][CH2:19][CH3:20])=[O:17])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCOC(=O)[C@H]1[C@H](C)OCC(=O)N1Cc1ccccc1
Solvent: C1CCOC1
Product: CCOC(=O)[C@H]1[C@H](C)OCCN1Cc1ccccc1
Temperature: 20 °C
Reaction time: 16 h
Yield: 105.2 %

Procedure:
To (2S,3R)-ethyl 4-benzyl-2-methyl-5-oxomorpholine-3-carboxylate (683 mg, 2.463 mmol) in THF (6 ml), BH3SMe2 (0.350 ml, 3.69 mmol) at 0° C. The reaction was stirred at 20° C. for 16 h. The reaction solution was quenched with water at 0° C. The layers were separated and the aqueous layer extracted with ethyl acetate. The combined organic layer washed with saturated NaCl. The organic was collected, dried with Na2SO4, filtered and concentrated in-vacuo to give a crude oil. The oil was purified by silica gel column chromatography (eluting with 10-20% gradient of EtOAc in hexanes using a Moritex SI-60 size 20 column). The resultant fractions were collected and concentrated in-vacuo to afford (2S,3R)-ethyl 4-benzyl-2-methylmorpholine-3-carboxylate (683 mg, 2.59 mmol, 105% yield (contained residual solvent)) as a colorless oil. MS [M+H] found 264.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:21]([O:23][CH3:24])=[O:22]>Cl.O1CCOCC1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:4][C:3]=1[C:21]([O:23][CH3:24])=[O:22]
Reactant: COC(=O)c1cc(C2CCN(C(=O)OC(C)(C)C)CC2)ccc1F
Agent: Cl
Solvent: C1COCCO1
Product: COC(=O)c1cc(C2CCNCC2)ccc1F
Temperature: 25 °C
Reaction time: 0.67 h

Procedure:
tert-Butyl 4-[4-fluoro-3-(methoxycarbonyl)phenyl]piperidine-1-carboxylate (471 mg, 1.40 mmol) was dissolved in anhydrous 4N HCl in dioxane (5mL) and stirred at r.t. for 40 min. The white solid was filtered and washed with Et2O to afford methyl 2-fluoro-5-piperidin-4-ylbenzoate.
Reaction SMILES: [N+]([C:4]1[CH:11]=[CH:10][CH:9]=[C:6]([C:7]#[N:8])[C:5]=1[C:12]#[N:13])([O-])=O.[F:14][C:15]([F:24])([F:23])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[OH:22].C(=O)([O-])[O-].[K+].[K+].CS(C)=O>O>[F:14][C:15]([F:23])([F:24])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[O:22][C:4]1[CH:11]=[CH:10][CH:9]=[C:6]([C:7]#[N:8])[C:5]=1[C:12]#[N:13]
Reactant: N#Cc1cccc([N+](=O)[O-])c1C#N
Reactant: Oc1ccccc1C(F)(F)F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: N#Cc1cccc(Oc2ccccc2C(F)(F)F)c1C#N
Temperature: 50 °C
Yield: 93.2 %

Procedure:
A reaction flask equipped with a cooling tube was loaded with 8.7 g of 3-nitrophthalonitrile, 9.4 g of 2-(trifluoromethyl)phenol, 13.8 g of anhydrous potassium carbonate and 350 ml of dimethyl sulfoxide, and the temperature was raised to 50° C. with stirring under nitrogen flow. After stirring at 50° C. for three hours, the heating was stopped. The reaction liquid was cooled and added into 500 ml of water, and the precipitated crystal was collected and dried to yield 13.5 g of the intended compound.
Reaction SMILES: C([O:3][C:4](=O)[C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:7][CH:6]=1)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].O>CCOCC>[CH2:11]([C:8]1[CH:7]=[CH:6][C:5]([CH2:4][OH:3])=[CH:10][CH:9]=1)[C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=1
Reactant: CCOC(=O)c1ccc(Cc2ccccc2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Solvent: O
Product: OCc1ccc(Cc2ccccc2)cc1
Reaction time: 1 h
Yield: 76.4 %

Procedure:
The above ester (4 g) in dry ether under nitrogen at 0° was treated with lithium aluminium hydride (0.9 g). After 1 hour at 0° and 18 hours at 25° water was added carefully and the mixture worked up in the usual manner to give 4-benzylbenzyl alcohol (2.52 g). NMR 1H: 7.21(9H,m), 4.53(2H,s), 3.95(2H,s), 2.10(1H,bs).
Reaction SMILES: [O:1]1[CH2:3][C:2]21[CH2:9][CH:8]1[N:10]([C:11]([O:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])[CH:5]([CH2:6][CH2:7]1)[CH2:4]2.C([O-])(O)=O.[Na+].C(OCC)(=O)C>O1CCCC1>[CH:3]([CH:2]1[CH2:4][CH:5]2[N:10]([C:11]([O:13][CH2:14][C:15]3[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=3)=[O:12])[CH:8]([CH2:7][CH2:6]2)[CH2:9]1)=[O:1]
Reactant: O=C(OCc1ccccc1)N1C2CCC1CC1(CO1)C2
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=CC1CC2CCC(C1)N2C(=O)OCc1ccccc1
Temperature: 4 °C
Reaction time: 3 h

Procedure:
To a cold (0° C.) solution of EXAMPLE 84A (3.5 g) in tetrahydrofuran (40 mL) was added boron trifluoride diethyl ether complex (0.82 mL). The mixture was stirred at 3-5° C. for 3 hours. Aqueous saturated NaHCO3 was added, followed by ethyl acetate (200 mL). The organic layer was separated, washed with water (twice) and concentrated to dryness. Toluene was added and the mixture was concentrated under vacuum to provide the title compound.
Reaction SMILES: [Cl:1][C:2]([O:4][C:5](Cl)(Cl)Cl)=[O:3].[C:9]([C:17]1[CH:18]=[CH:19][C:20]([N+:27]([O-:29])=[O:28])=[C:21]([CH:23](C)[CH2:24]O)[CH:22]=1)(=[O:16])[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C(N(CC)CC)C>O1CCCC1>[C:9]([C:17]1[CH:18]=[CH:19][C:20]([N+:27]([O-:29])=[O:28])=[C:21]([CH:23]([CH3:24])[CH2:5][O:4][C:2]([Cl:1])=[O:3])[CH:22]=1)(=[O:16])[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1
Reactant: O=C(Cl)OC(Cl)(Cl)Cl
Reactant: CC(CO)c1cc(C(=O)c2ccccc2)ccc1[N+](=O)[O-]
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CC(COC(=O)Cl)c1cc(C(=O)c2ccccc2)ccc1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of trichloromethyl chloroformate (15.83 g, 80 mmol, 0.8 equivalents) in dry tetrahydrofuran (150 mL), which has been pre-cooled to 0° C., was added over a period of approximately 2 hours a solution of 2-(5-benzoyl-2-nitrophenyl)-1-propanol (4f) (28.53 g, 100 mmol) and triethylamine (10.12 g, 100 mmol) in tetrahydrofuran (250 mL) with continued cooling. After stirring for 1 hour at ambient temperature the resulting suspension was filtered, the filter cake was washed with a little tetrahydrofuran, and the combined organic phases were concentrated in vacuo to give 19f as yellow oil.
Reaction SMILES: [CH3:1][C:2]1[CH:19]=[CH:18][C:5]([NH:6][C:7]2[S:8][C:9]3[N:17]=[CH:16][CH:15]=[CH:14][C:10]=3[C:11](=[O:13])[N:12]=2)=[CH:4][CH:3]=1.[H-].[Li+].[CH3:22]I>>[CH3:22][N:12]1[C:11](=[O:13])[C:10]2[CH:14]=[CH:15][CH:16]=[N:17][C:9]=2[S:8][C:7]1=[N:6][C:5]1[CH:18]=[CH:19][C:2]([CH3:1])=[CH:3][CH:4]=1
Reactant: Cc1ccc(Nc2nc(=O)c3cccnc3s2)cc1
Reactant: CI
Agent: [H-]
Agent: [Li+]
Product: Cc1ccc(N=c2sc3ncccc3c(=O)n2C)cc1
Yield: 70 %

Procedure:
The reaction procedure of Example 11 was followed except that 949 mg (3.52 mmol) of 2-(4-methylanilino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one, 28 mg of lithium hydride and 500 mg of methyl iodide were used. The resulting residue was then purified through silica gel column chromatography (eluant: chloroform) to obtain 698 mg of 2,3-dihydro-3-methyl-2-[(4-methylphenyl)imino]-4H-pyrido[3,2-e]-1,3-thiazin-4-one (70%, recrystallized from a mixture of ether and hexane).
Reaction SMILES: [CH3:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([CH3:11])=[CH:10][C:5]2=[N:4][C:3]=1[C:12]1[CH:17]=[CH:16][C:15]([NH:18][C:19](=O)[CH3:20])=[C:14]([N+:22]([O-])=O)[CH:13]=1.[H][H]>CO.[Pd]>[CH3:1][C:2]1[N:6]2[CH:7]=[CH:8][C:9]([CH3:11])=[CH:10][C:5]2=[N:4][C:3]=1[C:12]1[CH:17]=[CH:16][C:15]2[N:18]=[C:19]([CH3:20])[NH:22][C:14]=2[CH:13]=1
Reactant: [H][H]
Reactant: CC(=O)Nc1ccc(-c2nc3cc(C)ccn3c2C)cc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CO
Product: Cc1ccn2c(C)c(-c3ccc4nc(C)[nH]c4c3)nc2c1
Reaction time: 8 h
Yield: 29.9 %

Procedure:
A mixture of 3,7-dimethyl-2-(4-acetoamido-3-nitrophenyl)imidazo[1,2-a]pyridine (2 g) in methanol (200 ml) was hydrogenated over 10% palladium on carbon (wet, 400 mg) under an atmospheric pressure of hydrogen at ambient temperature for 2 hours. The catalyst was filtered off and the filtrate was concentrated to 20 ml of volume and allowed to stand overnight. Th.e precipitates were filtered off and the filtrate was concentrated under reduced pressure. The residue was subjected to column chromatography on aluminum oxide (50 g) eluting with chloroform. The fractions containing the object compound were combined and allowed to stand overnight. The resultant yellow needles were collected by filtration and dried under reduced pressure to afford 5-(3,7-dimethylimidazo[1,2-a]pyridin-2-yl)-2-methylbenzimidazole (0.51 g). mp. 250°-253° C. (dec.).
Reaction SMILES: [Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1OS(C(F)(F)F)(=O)=O.[NH2:27][CH:28]1[CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29]1>>[Cl:1][C:2]1[CH:18]=[CH:17][C:5]2[CH2:6][CH2:7][N:8]([C:11](=[O:16])[C:12]([F:15])([F:14])[F:13])[CH2:9][CH2:10][C:4]=2[C:3]=1[NH:27][CH:28]1[CH2:36][C:35]2[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=2)[CH2:29]1
Reactant: O=C(N1CCc2ccc(Cl)c(OS(=O)(=O)C(F)(F)F)c2CC1)C(F)(F)F
Reactant: NC1Cc2ccccc2C1
Product: O=C(N1CCc2ccc(Cl)c(NC3Cc4ccccc4C3)c2CC1)C(F)(F)F

Procedure:
Use a method similar to the General Procedure 5-3, using 7-chloro-3-(2,2,2-trifluoroacetyl)-6-trifluoromethanesulfonyloxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (426 mg, 1.0 mmol) and 2-aminoindane (400 mg, 3.0 mmol), to give 7-chloro-6-(indan-2-yl-amino)-3-(2,2,2-trifluoroacetyl)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as a slightly yellow oil (354 mg, 86%). MS (ES+) m/z: 409 (M+H)+.
Reaction SMILES: C[O-].[Na+].Cl.[NH2:5][CH2:6][C:7](=O)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.[N+:16]([CH:19]=[C:20](SC)[S:21]([CH3:23])=O)([O-:18])=[O:17]>CO>[CH3:23][S:21][C:20]1[NH:5][CH:6]=[C:7]([CH2:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:19]=1[N+:16]([O-:18])=[O:17]
Reactant: NCC(=O)Cc1ccccc1
Reactant: CSC(=C[N+](=O)[O-])S(C)=O
Agent: C[O-]
Agent: Cl
Agent: [Na+]
Solvent: CO
Product: CSc1[nH]cc(Cc2ccccc2)c1[N+](=O)[O-]
Reaction time: 0.42 h
Yield: 28.3 %

Procedure:
A solution of sodium methoxide (sodium (1.9g, 0.084 mol) dissolved in methanol (100 ml)) and a solution of 1-amino-3-phenylpropan-2-one hydrochloride (7.9g, 0.042 mol) in methanol (100 ml) were simultaneously added dropwise, to a stirred solution of 1-nitro-2-methylthio-2-methylsulphinyl-ethylene (7.7g, 0.042 mol) in methanol. The temperature was maintained at about 60° during the addition, which took 25 minutes. The solvent was then removed in vacuo, and the residual dark red oil was chromatographed on a silica gel column. Elution and recrystallisation with petroleum ether/ethyl acetate (7:3) gave 2-methylthio-3-nitro-4-benzylpyrrole (2.95g, 28.5%) m.p. 190-192.5°.