Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OC([N:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH:12]1[C:17]1[O:18][C:19]([C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[CH:20][N:21]=1)=O)C1C=CC=CC=1.C[Si](I)(C)C.CO>C(Cl)(Cl)Cl>[C:22]1([C:19]2[O:18][C:17]([CH:12]3[CH2:13][CH2:14][CH2:15][CH2:16][NH:11]3)=[N:21][CH:20]=2)[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: O=C(OCc1ccccc1)N1CCCCC1c1ncc(-c2ccccc2)o1
Agent: C[Si](C)(C)I
Solvent: CO
Solvent: ClC(Cl)Cl
Product: c1ccc(-c2cnc(C3CCCCN3)o2)cc1
Temperature: 25 °C
Reaction time: 5 h
Yield: 58.7 %

Procedure:
To a solution of 0.56 g (1.5 mmol) of 2-(5-Phenyl-oxazol-2-yl)-piperidine-1-carboxylic acid benzyl ester in 5 mL of chloroform, cooled in an ice bath under argon, was added 5 mL of trimethylsilyliodide. The mixture was allowed to slowly warm to room temperature and stir for five hours. To the reaction mixture was added 10 mL of methanol and the resulting mixture was allowed to stir at room temperature for 0.5 hour. The resulting mixture was partitioned between diethyl ether and 2N hydrochloric acid. The aqueous layer was separated, basified with 2N sodium hydroxide and extracted twice with diethyl ether. The combined ethyl ether extracts were dried over magnesium sulfate and concentrated to 0.20 g (0.88 mmol, 58% yield) of a yellow oil. The oil was 98% pure by LC analysis.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[C:7]1([CH3:23])[CH:12]=[CH:11][C:10]([N:13]=[C:14]=[N:15][C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=2)=[CH:9][CH:8]=1>CN(C=O)C>[C:19]1([CH3:22])[CH:20]=[CH:21][C:16]([NH:15][C:14]([N:1]2[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]2)=[N:13][C:10]2[CH:9]=[CH:8][C:7]([CH3:23])=[CH:12][CH:11]=2)=[CH:17][CH:18]=1
Reactant: Cc1ccc(N=C=Nc2ccc(C)cc2)cc1
Reactant: C1CNCCN1
Solvent: CN(C)C=O
Product: Cc1ccc(N=C(Nc2ccc(C)cc2)N2CCNCC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 52 %

Procedure:
1.2 mmol of piperazine was dissolved in 10 ml of DMF and 1.0 mmol of 1,3-di-p-tolylcarbodiimide was added. After 0.5 hour of stirring at room temperature, a small precipitation was filtered off, and washed twice with 1 ml of DMF. The filtrates were collected and kept at room temperature overnight. 50 ml of water was added to the solution. A precipitated oil was separated by centrifugation. The residual oil was dissolved in 10 ml of methanol and 0.2 ml of conc. HCl was added. The methanol solution was concentrated to 2 ml and purified by gel filtration on Sephadex LH-20 in methanol. Yield=52%.
Reaction SMILES: [CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]([C:13]1[CH:18]=[CH:17][C:16]([OH:19])=[CH:15][CH:14]=1)[C:6]([O:8][C:9]([CH3:12])([CH3:11])[CH3:10])=[O:7].C(=O)([O-])[O-].[K+].[K+].Br[CH2:28][CH2:29][CH2:30][N:31]1[C:35](=[O:36])[C:34]2=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]2[C:32]1=[O:41]>CN(C=O)C>[CH3:1][O:2][C:3](=[O:20])[CH2:4][N:5]([C:13]1[CH:18]=[CH:17][C:16]([O:19][CH2:28][CH2:29][CH2:30][N:31]2[C:35](=[O:36])[C:34]3=[CH:37][CH:38]=[CH:39][CH:40]=[C:33]3[C:32]2=[O:41])=[CH:15][CH:14]=1)[C:6]([O:8][C:9]([CH3:12])([CH3:10])[CH3:11])=[O:7]
Reactant: COC(=O)CN(C(=O)OC(C)(C)C)c1ccc(O)cc1
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: COC(=O)CN(C(=O)OC(C)(C)C)c1ccc(OCCCN2C(=O)c3ccccc3C2=O)cc1
Temperature: 100 °C

Procedure:
To 10 ml of anhydrous DMF were added 2.8 g of N- Boc-p-hydroxyphenylglycine methyl ester and 1.38 g (1.0 eq) of anhydrous potassium carbonate, followed by addition of 2.68 g (1.0 eq.) of N-(3-bromopropyl)phthalimide. The mixture was heated at 100° C. for 1 hour. The reaction mixture was poured into ice water, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and a saturated aqueous solution of sodium chloride, and dried. Thereafter, the solvent was distilled off. The residue was purified by silica gel column chromatography (eluent: 5% ethyl acetate/dichloromethane), to give colorless crystals.
Reaction SMILES: [NH2:1][CH2:2][C:3]1([N:9]([CH3:11])[CH3:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.[C:12]([Cl:20])(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1>N1C=CC=CC=1>[ClH:20].[C:12]([NH:1][CH2:2][C:3]1([N:9]([CH3:11])[CH3:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: O=C(Cl)c1ccccc1
Reactant: CN(C)C1(CN)CCCCC1
Solvent: c1ccncc1
Product: CN(C)C1(CNC(=O)c2ccccc2)CCCCC1
Product: Cl
Reaction time: 1 h

Procedure:
A mixture of 1-aminomethylcyclohexyldimethylamine (1.5 g), benzoyl chloride (3 ml) and pyridine (10 ml) was allowed to stand at room temperature for 1 hr. The crystalline mass was filtered and recrystallised several times from 95% ethanol to give colourless prisms of 1-benzamidomethylcyclohexyldimethylamine hydrochloride m.p. 245°-6° .
Reaction SMILES: [C:1]([OH:14])(=[O:13])[C:2]1[CH:12]=[C:9]([O:10][CH3:11])[C:7]([OH:8])=[C:4]([O:5][CH3:6])[CH:3]=1.[CH2:15](Br)[C:16]#[CH:17]>>[CH2:17]([O:13][C:1](=[O:14])[C:2]1[CH:3]=[C:4]([O:5][CH3:6])[C:7]([OH:8])=[C:9]([O:10][CH3:11])[CH:12]=1)[C:16]#[CH:15]
Reactant: COc1cc(C(=O)O)cc(OC)c1O
Reactant: C#CCBr
Product: C#CCOC(=O)c1cc(OC)c(O)c(OC)c1

Procedure:
By utilizing the procedure of Example 5, by reacting syringic acid and propargyl bromide, there is obtained syringic acid propargyl ester, F.P. 105°-106° C.
Reaction SMILES: [F:1][C:2]([F:18])([F:17])[S:3]([O:6][CH2:7][CH2:8][O:9][Si:10]([C:13]([CH3:16])([CH3:15])[CH3:14])([CH3:12])[CH3:11])(=[O:5])=[O:4].[CH2:19]([O:22][C:23]([N:25]1[C@H:29]([CH2:30][C:31]2[S:35][C:34]3=[CH:36][N:37]=[CH:38][N:33]3[CH:32]=2)[CH2:28][C@H:27]([S:39][C:40]2[C@H:41]([CH3:57])[C@@H:42]3[C@@H:52]([C@H:53]([OH:55])[CH3:54])[C:51](=[O:56])[N:43]3[C:44]=2[C:45]([O:47][CH2:48][CH:49]=[CH2:50])=[O:46])[CH2:26]1)=[O:24])[CH:20]=[CH2:21]>ClC(Cl)C>[F:1][C:2]([F:18])([F:17])[S:3]([O-:6])(=[O:5])=[O:4].[CH2:19]([O:22][C:23]([N:25]1[C@H:29]([CH2:30][C:31]2[S:35][C:34]3=[CH:36][N:37]([CH2:7][CH2:8][O:9][Si:10]([C:13]([CH3:14])([CH3:15])[CH3:16])([CH3:11])[CH3:12])[CH:38]=[N+:33]3[CH:32]=2)[CH2:28][C@H:27]([S:39][C:40]2[C@H:41]([CH3:57])[C@@H:42]3[C@@H:52]([C@H:53]([OH:55])[CH3:54])[C:51](=[O:56])[N:43]3[C:44]=2[C:45]([O:47][CH2:48][CH:49]=[CH2:50])=[O:46])[CH2:26]1)=[O:24])[CH:20]=[CH2:21]
Reactant: CC(C)(C)[Si](C)(C)OCCOS(=O)(=O)C(F)(F)F
Reactant: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](Cc3cn4cncc4s3)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Solvent: CC(Cl)Cl
Product: C=CCOC(=O)C1=C(S[C@H]2C[C@@H](Cc3c[n+]4cn(CCO[Si](C)(C)C(C)(C)C)cc4s3)N(C(=O)OCC=C)C2)[C@H](C)[C@@H]2[C@@H]([C@@H](C)O)C(=O)N12
Product: O=S(=O)([O-])C(F)(F)F
Temperature: 25 °C
Reaction time: 2 h

Procedure:
2-(t-Butyldimethylsilyloxy)ethyl trifluoromethanesulfonate (20.9 mg) is added to a solution of 32.3 mg of allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-(imidazo[5,1-b]thiazol-2-yl)methylpyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate described in Example 23-a) in 0.5 ml of dry dichloroethane, and the mixture is stirred in an argon atmosphere at room temperature for 2 hr. The excess reagent is removed by evaporation under reduced pressure to give allyl(1R,5S,6S)-2-[(3S,5S)-1-allyloxycarbonyl-5-[6-(2-t-butyldimethylsilyloxyethyl)imidazo[5,1-b]thiazolium-2-yl]methylpyrrolidin-3-yl]thio-6-((1R)-1-hydroxyethyl)-1-methylcarbapen-2-em-3-carboxylate trifluoromethanesulfonate as a brown viscous material.
Reaction SMILES: C[O-].[Na+:3].[F:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[CH:18]=[C:17]([S:22](CCC#N)(=[O:24])=[O:23])[CH:16]=[CH:15]2>O1CCCC1.CO.C(OCC)C>[F:4][C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:6]=1[C:12]1[CH:13]=[C:14]2[C:19](=[CH:20][CH:21]=1)[CH:18]=[C:17]([S:22]([O-:24])=[O:23])[CH:16]=[CH:15]2.[Na+:3]
Reactant: N#CCCS(=O)(=O)c1ccc2cc(-c3ccc(F)cc3F)ccc2c1
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: CO
Solvent: CCOCC
Product: O=S([O-])c1ccc2cc(-c3ccc(F)cc3F)ccc2c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 97.1 %

Procedure:
Sodium methoxide (0.68 g, 12.6 mmol) was added to a solution of 3-{[6-(2,4-difluorophenyl)-2-naphthyl]sulfonyl}propanenitrile (Step 2, 4.04 g, 11.3 mmol) in tetrahydrofuran/methanol (1:1, 120 mL) and stirred at room temperature under nitrogen for 1 hour. The reaction mixture was diluted with diethyl ether (120 mL) and stirred for 30 minutes. The solid precipitate was collected by filtration to give sodium 6-(2,4-difluorophenyl)naphthalene-2-sulfinate (3.58 g). 1H NMR (500 MHz, CD3OD) δ 8.14 (1H, s), 8.03-7.97 (3H, m), 7.84 (1H, d, J=8.4 Hz), 7.66 (2H, dd, J=8.6, 20.2 Hz), 7.10-7.08 (2H, m).
Reaction SMILES: [C:1]1(/[CH:7]=[CH:8]/[CH2:9][NH:10][C@H:11]([CH3:37])[C@@H:12]([C:28]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=2)[CH2:13][C:14]2[O:15][C:16]([C:19](=[O:27])[NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[OH:38][C@H:39]([CH3:61])[C@H:40]([C:52]1[CH:57]=[CH:56][C:55]([N+:58]([O-:60])=[O:59])=[CH:54][CH:53]=1)[CH2:41][C:42]1[O:46][C:45]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:44][CH:43]=1>>[C:1]1(/[CH:7]=[CH:8]/[CH2:9][NH:10][C@@H:11]([CH3:37])[C@H:12]([C:28]2[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=2)[CH2:13][C:14]2[O:15][C:16]([C:19](=[O:27])[NH:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:17][CH:18]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:14]([O:38][C@H:39]([CH3:61])[C@H:40]([C:52]1[CH:53]=[CH:54][C:55]([N+:58]([O-:60])=[O:59])=[CH:56][CH:57]=1)[CH2:41][C:42]1[O:46][C:45]([C:47]([O:49][CH2:50][CH3:51])=[O:48])=[CH:44][CH:43]=1)(=[O:15])[CH3:13]
Reactant: CCOC(=O)c1ccc(C[C@@H](c2ccc([N+](=O)[O-])cc2)[C@@H](C)O)o1
Reactant: C[C@@H](NC/C=C/c1ccccc1)[C@H](Cc1ccc(C(=O)Nc2ccccc2)o1)c1ccc([N+](=O)[O-])cc1
Product: CCOC(=O)c1ccc(C[C@@H](c2ccc([N+](=O)[O-])cc2)[C@@H](C)OC(C)=O)o1
Product: C[C@H](NC/C=C/c1ccccc1)[C@@H](Cc1ccc(C(=O)Nc2ccccc2)o1)c1ccc([N+](=O)[O-])cc1

Procedure:
N-{(E)-3-Phenyl-2-propenyl}-[(1S,2S)-1-methyl-2-(4-nitrophenyl)-3-{5-(phenylcarbamoyl)-2-furyl}propyl]amine was prepared in the same manner as in (2) from ethyl 5-{(2S,3R)-3-hydroxy-2-(4-nitrophenyl)butyl}-2-furancarboxylate obtained by alkali hydrolysis of ethyl 5-{(2S,3R)-3-acetoxy-2-(4-nitrophenyl)butyl}-2-furancarboxylate prepared in (1) as described above.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([CH2:9][CH3:10])[CH:6]=[C:5]([CH2:11][CH3:12])[C:4]=1[C:13](=[O:19])[C:14]([N:16]([CH3:18])[NH2:17])=[O:15])[CH3:2].[F:20][C:21]([F:28])([F:27])[C:22](=O)[CH2:23][S:24][CH3:25].O>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]([C:3]1[CH:8]=[C:7]([CH2:9][CH3:10])[CH:6]=[C:5]([CH2:11][CH3:12])[C:4]=1[C:13](=[O:19])[C:14]([N:16]([CH3:18])[N:17]=[C:22]([CH2:23][S:24][CH3:25])[C:21]([F:28])([F:27])[F:20])=[O:15])[CH3:2]
Reactant: CCc1cc(CC)c(C(=O)C(=O)N(C)N)c(CC)c1
Reactant: CSCC(=O)C(F)(F)F
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: O
Product: CCc1cc(CC)c(C(=O)C(=O)N(C)N=C(CSC)C(F)(F)F)c(CC)c1
Temperature: 25 °C
Yield: 50 %

Procedure:
To a 100 ml volume three-necked flask, 1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-1-methylhydrazine ((12-2)-(11)-40) (3.01 g) was added, and to the mixture was added dropwise a solution of 1,1,1-trifluoro-3-methylsulfanyl-2-propanone (7-0-2) (2.10 g) in toluene (27 g), followed by the addition of para-toluenesulfonic acid monohydrate (0.030 g). The resulting mixture was stirred under reflux for 40 minutes. Then, the reaction mixture was cooled to room temperature, poured into water (30 ml), and extracted with ethyl acetate (50 ml) 3 times. The resulting organic layer was dried over magnesium sulfate, concentrated under reduced pressure, and subjected to silica gel column chromatography (chloroform) to give 2.31 g of 1-[2-(2,4,6-triethylphenyl)-2-oxoacetyl]-2-(1,1,1-trifluoro-3-methylsulfanyl-2-propylidene)-1-methylhydrazine ((4-46)-(1)-40).
Reaction SMILES: [H-].[Na+].[C:3]1([CH3:13])[CH:8]=[CH:7][C:6]([S:9]([NH2:12])(=[O:11])=[O:10])=[CH:5][CH:4]=1.Br[CH2:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][C:17]=1[CH2:23]Br>CN(C=O)C>[Cl:22][C:19]1[CH:18]=[C:17]2[C:16](=[CH:21][CH:20]=1)[CH2:15][N:12]([S:9]([C:6]1[CH:5]=[CH:4][C:3]([CH3:13])=[CH:8][CH:7]=1)(=[O:10])=[O:11])[CH2:23]2
Reactant: Cc1ccc(S(N)(=O)=O)cc1
Reactant: Clc1ccc(CBr)c(CBr)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc(S(=O)(=O)N2Cc3ccc(Cl)cc3C2)cc1
Temperature: 25 °C
Yield: 64.2 %

Procedure:
To a suspension of 60% sodium hydride (3.0 g, 0.125 mmol) in mineral oil in 80 ml of anhydrous DMF (100 ml) was dropwise added a solution of para-toluene sulphonamide (5.6 g, 32.60 mmol) in 30 ml of DMF over 1 hour with vigorous stirring at room temperature. After the addition, the mixture was stirred for 1 hour at room temperature and another 1 hour heating at 90° C. To this mixture was added dropwise a solution of 1,2-bis-bromomethyl-4-chloro-benzene (4 g, 14.18 mmol) in 20 ml of anhydrous DMF at 60° C. and then stirred overnight at room temperature. The resultant mixture was poured onto ice and the resulting precipitate was collected by filtration. The precipitate was washed with 1N hydrochloric acid, 5% sodium carbonate and brine then dried (MgSO4), filtered and evaporated to give 2.8 g of 5-Chloro-2-(toluene-4-sulphonyl)-2,3-dihydro-1H-isoindole as a pale yellow solid. MS: [M+H]+ 308
Reaction SMILES: [CH3:1][C:2]([Si:5]([CH3:12])([CH3:11])[O:6][CH:7]1[CH2:10][NH:9][CH2:8]1)([CH3:4])[CH3:3].C(N(CC)C(C)C)(C)C.[CH3:22][C:23]([O:26][C:27]([N:29]1C(C2C=CC(C#N)=CC=2)O1)=[O:28])([CH3:25])[CH3:24]>ClCCl>[C:23]([O:26][C:27](=[O:28])[NH:29][N:9]1[CH2:10][CH:7]([O:6][Si:5]([C:2]([CH3:1])([CH3:3])[CH3:4])([CH3:12])[CH3:11])[CH2:8]1)([CH3:25])([CH3:24])[CH3:22]
Reactant: CC(C)(C)OC(=O)N1OC1c1ccc(C#N)cc1
Reactant: CC(C)(C)[Si](C)(C)OC1CNC1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NN1CC(O[Si](C)(C)C(C)(C)C)C1
Temperature: 0 °C
Reaction time: 1 h
Yield: 73.5 %

Procedure:
3-[[(1,1-Dimethylethyl)dimethylsilyl]oxy]-azetidine (300 mg, 1.6 mmol) was combined with dichloromethane (16 mL) to give a brown solution. N,N-Diisopropylethylamine (455 mg, 615 μl, 3.52 mmol) was added at 0° C. Subsequently 3-(4-cyanophenyl)-2-oxaziridinecarboxylic acid 1,1-dimethylethyl ester (355 mg, 1.44 mmol) in dichloromethane (10 mL) was added during 25 min at 0° C. and the reaction mixture was stirred for 1 h at 0° C. Afterwards the reaction mixture was concentrated in vacuo and the residue was purified by flash chromatography (silica gel, 20 g, 0% to 40% ethyl acetate in n-heptane) to deliver an oil contaminated with 4-cyano-benzaldehyde. This material was purified by a second chromatography (aminophase 12 g, ethyl acetate/n-heptane 1/1) to give the title compound (320 mg, 67%) as white waxy solid; GC-MS (EI) 302.0 (M)+.
Reaction SMILES: [C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1)#[N:2].[CH3:12][N:13]([NH2:21])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(N(CC)CC)C>ClCCl>[C:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:21][N:13]([CH3:12])[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:8])=[CH:5][CH:4]=1)#[N:2]
Reactant: N#Cc1ccc(C(=O)Cl)cc1
Reactant: CN(N)C(=O)OC(C)(C)C
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CN(NC(=O)c1ccc(C#N)cc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 2 h
Yield: 66.4 %

Procedure:
A solution of 4-cyanobenzoyl chloride (2.5 g) in dichloromethane (50 ml) was added dropwise with stirring over 45 minutes to an ice-cold solution of t-butyl 2-methylcarbazate (2.0 g) in dichloromethane (50 ml) containing triethylamine (1.9 ml). The reaction mixture was stirred at ambient temperature for 2 hours and then washed with water, dilute aqueous sodium bicarbonate solution and brine, dried (MgSO4) and evaporated. The residue was crystallised from ethyl acetate to give t-butyl 3-(4-cyanobenzoyl)-2-methyl-carbazate (2.5 g) as a white solid; m.p. 179°-181° C.; NMR Spectrum (DMSO--d6) 1.27-1.55 (9H, br s), 3.10 (3H, br s), 8.00 (4H, s), 10.90 (1H, s); Mass Spectrum m/Z 276 (M+H)+ ; Elemental Analysis: calculated for C14H17N3O3 : C, 61.1%; H, 6.2%; N, 15.3%; found: C, 61.6%; H, 6.2%; N, 15.5%.
Reaction SMILES: Cl[C:2]1[C:11]2[N:12]=[C:13]([CH2:29][O:30][CH2:31][CH3:32])[N:14]([CH2:15][CH2:16][CH2:17][C:18]3[O:22][N:21]=[C:20]([C:23]4[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=4)[CH:19]=3)[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH3:33]>CO>[CH2:31]([O:30][CH2:29][C:13]1[N:14]([CH2:15][CH2:16][CH2:17][C:18]2[O:22][N:21]=[C:20]([C:23]3[CH:24]=[N:25][CH:26]=[CH:27][CH:28]=3)[CH:19]=2)[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:33])[C:11]=2[N:12]=1)[CH3:32]
Reactant: CCOCc1nc2c(Cl)nc3ccccc3c2n1CCCc1cc(-c2cccnc2)no1
Reactant: N
Solvent: CO
Product: CCOCc1nc2c(N)nc3ccccc3c2n1CCCc1cc(-c2cccnc2)no1

Procedure:
A slurry of 4-chloro-2-(ethoxymethyl)-1-[3-(3-pyridin-3-ylisoxazol-5-yl)propyl]-1H-imidazo[4,5-c]quinoline (1.78 g, 3.97 mmol) in a solution of 7 M ammonia in methanol (20 mL) was heated at 150° C. for 20 hours in a Parr pressure vessel. The volatiles were removed under reduced pressure and the resulting oil was partitioned between dichloromethane and 1 M KOH. The aqueous layer was extracted with dichloromethane. The organic layers were combined, washed with water and brine, dried over magnesium sulfate, filtered, and concentrated. The crude product was purified by flash chromatography (silica gel, gradient elution from 9:1 to 4:1 chloroform/CMA). After concentration of the appropriate fractions, a white solid was obtained. The white solid was triturated with diethyl ether and dried at 80° C. under vacuum to provide 2-(ethoxymethyl)-1-[3-(3-pyridin-3-ylisoxazol-5-yl)propyl]-1H-imidazo[4,5-c]quinolin-4-amine as a white powder, mp 199.0-200.0° C.
Reaction SMILES: [CH:1]([NH2:4])([CH3:3])[CH3:2].[OH:5]C[C:7]([CH2:13][OH:14])([CH2:11]O)[N+]([O-])=O.C=O>>[CH3:2][CH:1]([OH:5])[CH3:3].[O:14]1[CH:13]=[CH:7][CH:11]=[CH:1][NH:4]1
Reactant: CC(C)N
Reactant: O=[N+]([O-])C(CO)(CO)CO
Agent: C=O
Product: C1=CNOC=C1
Product: CC(C)O
Temperature: 17 °C

Procedure:
A 2-liter, 3-neck round bottom flask equipped with a nitrogen blanket, addition funnel, mechanical stirrer and thermocouple was charged with isopropylamine (425 mL, 5.0 mol). The addition funnel was charged with a pre-dissolved mixture of tris(hydroxymethyl)nitromethane (TN®)(377.75 g, 2.5 mol) in 37% aqueous formaldehyde (202.9 g, 2.5 mol) and the reactor contents cooled to 15 C with a cold water bath. The TN/formaldehyde solution was added dropwise to the isopropylamine over a period of 1.5 hours while maintaining an internal reaction temperature of 15-19° C. After the addition was complete, the cooling bath was removed. The mixture changed from a clear solution to a water/oil emulsion and slowly warmed to 34° C. over 40 minutes. A heating mantle was then used to warm the mixture to 70° C. for 5 hours. The reaction mass was then allowed to cool back to room temperature overnight. The reaction product had partially solidified to a yellow paste. Hexane (750 mL) was then added and the water was azeotropically removed. As the last of the water was removed, a white solid precipitated. The slurry was placed in the freezer overnight to complete crystallization. The white, crystalline hexahydropyrimidine product was recovered via filtration, 245 g, 39.9% of theory. The hexane layer was concentrated on a rotary evaporation to yield the oxazine (IPA-OZ) as a yellow oil (approximately 370 g, 60% of theory). Note: Over a period of weeks, the oxazine will slowly convert to the hexahydropyrimidine as evidenced by its crystallization from the oil.
Reaction SMILES: Cl[C:2]1[N:10]=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=O.S(Cl)(Cl)=O.[S-:15][C:16]#[N:17].[NH4+].[CH3:19][NH:20][CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>CC(C)=O.CN(C=O)C>[CH3:19][N:20]([C:16]1[S:15][C:2]2[N:10]=[CH:9][CH:8]=[CH:7][C:3]=2[C:4](=[O:6])[N:17]=1)[CH2:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: CNCCc1ccccc1
Reactant: N#C[S-]
Reactant: O=C(O)c1cccnc1Cl
Agent: [NH4+]
Solvent: CN(C)C=O
Solvent: O=S(Cl)Cl
Solvent: CC(C)=O
Product: CN(CCc1ccccc1)c1nc(=O)c2cccnc2s1
Yield: 56.5 %

Procedure:
The reaction procedure of Example 57 was followed except that 1.792 g (11.37 mmol) of 2-chloronicotinic acid, 15 ml of thionyl chloride, two droplets of DMF, 909 mg of ammonium thiocyanate, 15 ml of acetone, 1.61 g of N-methylphenethylamine and 10 ml of acetone were used. The product was then recrystallized from ethanol to obtain 1.91 g of 2-(N-methyl-N-phenethylamino)-4H-pyrido[3,2-e]-1,3-thiazin-4-one.
Reaction SMILES: C(Cl)(=O)OCC.[OH:7][C:8]1[C:16]([CH2:17][CH2:18][CH3:19])=[C:15]([O:20][CH3:21])[CH:14]=[CH:13][C:9]=1[C:10]([OH:12])=O.[S:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[CH2:27][NH2:28].Cl>C(Cl)Cl.C(N(CC)CC)C>[OH:7][C:8]1[C:16]([CH2:17][CH2:18][CH3:19])=[C:15]([O:20][CH3:21])[CH:14]=[CH:13][C:9]=1[C:10]([NH:28][CH2:27][C:23]1[S:22][CH:26]=[CH:25][CH:24]=1)=[O:12]
Reactant: CCCc1c(OC)ccc(C(=O)O)c1O
Reactant: NCc1cccs1
Agent: CCOC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCc1c(OC)ccc(C(=O)NCc2cccs2)c1O
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
Under argon atmosphere, a solution of ethyl chlorocarbonate (7.65 ml) in methylene chloride (90 ml) was cooled to -15° C., and to the solution was added dropwise a solution of 2-hydroxy-3-n-propyl-4-methoxybenzoic acid (8 g) and triethylamine (11.1 ml) in methylene chloride (160 ml) for 30 minutes, and the mixture was agitated for another 15 minutes. 2-thiophenemethylamine (4.7 ml) was added to the mixture and the mixture was agitated for 3 hours while the temperature of the mixture was elevated to 0° C. The reaction mixture was poured into 1N aqueous hydrochloric acid, and extracted with methylene chloride. The organic layer was washed with a mixed solution of saturated aqueous solution of sodium chloride and saturated aqueous solution of sodium bicarbonate, dried over anhydrous magnesium sulfate, and concentrated in evacuated atomosphere. The residue was dissolve in methanol (100 ml), and the solution was cooled to 0° C. The solution was added to 8.5% aqueous solution of sodium hydroxide (50 ml) and the mixture was agitated at room temperature for 4.5 hours. The reaction mixture was acidified by adding 6N aqueous hydrochloric acid thereto, and extracted twice with ethyl acetate. The organic layer was washed with saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and concentrated in evacuated atomosphere. The residue was subjected to column chromatography using silica gel, and there was obtained N-(2-hydroxy-3-n-propyl-4-methoxybenzoyl)-2-thiophenemethylamine (5.7 g) from fractions eluted with n-hexane-methylene chloride (2:1).