Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([Li])CCC.[CH:6]([C:9]1[C:10]([CH:17]([CH3:19])[CH3:18])=[C:11]([CH:14]([CH3:16])[CH3:15])[CH2:12][CH:13]=1)([CH3:8])[CH3:7].S(C1C=CC(C)=CC=1)(O[CH2:24][CH2:25][N:26]([CH3:28])[CH3:27])(=O)=O.O>O1CCCC1>[CH3:27][N:26]([CH2:25][CH2:24][C:13]1[CH2:12][C:11]([CH:14]([CH3:16])[CH3:15])=[C:10]([CH:17]([CH3:19])[CH3:18])[C:9]=1[CH:6]([CH3:8])[CH3:7])[CH3:28]
Reactant: CC(C)C1=CCC(C(C)C)=C1C(C)C
Reactant: Cc1ccc(S(=O)(=O)OCCN(C)C)cc1
Agent: [Li]CCCC
Solvent: C1CCOC1
Solvent: O
Product: CC(C)C1=C(C(C)C)C(C(C)C)=C(CCN(C)C)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
In a dry 500 mL three-necked flask with a magnetic stirrer, a solution of 62.5 mL of n-butyllithium (1.6 M in n-hexane; 100 mmol) was added under a dry nitrogen atmosphere to a solution of 19.2 g (100 mmol) of triisopropyl-cyclopentadiene in 250 mL of tetrahydrofuran at -60° C. After heating to room temperature (in approximately one hour) stirring continued for a further two hours. After cooling to -60° C., a solution of dimethylaminoethyl tosylate (105 mmol) prepared in situ was added over a period of 5 minutes. The reaction mixture was heated to room temperature, followed by overnight stirring. After addition of water, the product was extracted with petroleum ether (40-60° C.). The combined organic layer was dried with sodium sulphate, and evaporated under reduced pressure. The conversion was greater than 95%. The yield of product after distillation (based on triisopropyl-cyclopentadiene) was approximately 55%.
Reaction SMILES: [CH3:1][NH:2][CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7].[CH3:8][C:9]([CH3:19])([CH3:18])[C@@H:10]([C:14]([O:16][CH3:17])=[O:15])[N:11]=[C:12]=[O:13]>O1CCCC1>[CH3:8][C:9]([CH3:19])([CH3:18])[C@@H:10]([C:14]([O:16][CH3:17])=[O:15])[NH:11][C:12]([N:2]([CH3:1])[CH2:3][CH2:4][CH2:5][CH:6]=[CH2:7])=[O:13]
Reactant: C=CCCCNC
Reactant: COC(=O)[C@@H](N=C=O)C(C)(C)C
Solvent: C1CCOC1
Product: C=CCCCN(C)C(=O)N[C@H](C(=O)OC)C(C)(C)C
Reaction time: 2 h
Yield: 55 %

Procedure:
A solution of N-methylpent-4-en-l-amine (2.0 g, 20.2 mmol) in tetrahydrofuran (20 mL) was stirred at room temperature under nitrogen. To this was added methyl 3-methyl-N-(oxomethylene)-L-valinate (3.5 g, 20.2 mmol) and the resulting solution stirred 2 h. Contents of the reaction flask were evaporated and subjected to flash column chromatography eluting with hexane/ethyl acetate 60/40 to give methyl 3-Methyl-N-{[methyl(pent-4-enyl)amino]carbonyl}-L-valinate as an orange oil, 3.02 g (55% yield).
Reaction SMILES: [C:1]([O:5][C:6]([C:9]([C:12]([O:15][C:16]([C:19](OC)=[O:20])([F:18])[F:17])([F:14])[F:13])([F:11])[F:10])([F:8])[F:7])([F:4])([F:3])[F:2].[NH:23]([CH2:25][C:26]([OH:28])=[O:27])[CH3:24].[OH-].[K+:30]>C(O)(C)C>[C:1]([O:5][C:6]([C:9]([C:12]([O:15][C:16]([C:19]([N:23]([CH2:25][C:26]([O-:28])=[O:27])[CH3:24])=[O:20])([F:18])[F:17])([F:14])[F:13])([F:10])[F:11])([F:7])[F:8])([F:3])([F:4])[F:2].[K+:30]
Reactant: CNCC(=O)O
Reactant: COC(=O)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)OC(F)(F)F
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Product: CN(CC(=O)[O-])C(=O)C(F)(F)OC(F)(F)C(F)(F)C(F)(F)OC(F)(F)F
Temperature: 60 °C

Procedure:
In a three-necked 100-mL flask fitted with a stirrer, thermometer, and condenser were placed 18 grams (0.05 mole) of CF3OCF2CF2CF2OCF2C(O)OCH3, prepared in Example 1, Part A, and dry sarcosine (4.5 grams, 0.05 mole). The reaction mixture was heated under nitrogen at 60° C. using a heating mantle for 48 hours and then cooled to about 30° C. Isopropanol (23 grams) and potassium hydroxide (2.8 grams, 0.05 mole) were added to provide a solution of CF3OCF2CF2CF2OCF2C(O)N(CH3)CH2C(O)O—K+.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([CH2:8][C:9]([C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)=O)[CH:5]=[CH:4][N:3]=1.CN(C=O)C.C1C(=O)N(Br)C(=O)C1.[CH3:43][CH:44]([CH3:48])[C:45](=[S:47])[NH2:46]>CCOC(C)=O>[Cl:1][C:2]1[N:7]=[C:6]([C:8]2[S:47][C:45]([CH:44]([CH3:48])[CH3:43])=[N:46][C:9]=2[C:11]2[C:12]([F:29])=[C:13]([NH:17][S:18]([C:21]3[C:26]([F:27])=[CH:25][CH:24]=[CH:23][C:22]=3[F:28])(=[O:20])=[O:19])[CH:14]=[CH:15][CH:16]=2)[CH:5]=[CH:4][N:3]=1
Reactant: O=C(Cc1ccnc(Cl)n1)c1cccc(NS(=O)(=O)c2c(F)cccc2F)c1F
Reactant: CC(C)C(N)=S
Agent: O=C1CCC(=O)N1Br
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: CC(C)c1nc(-c2cccc(NS(=O)(=O)c3c(F)cccc3F)c2F)c(-c2ccnc(Cl)n2)s1
Temperature: 25 °C
Reaction time: 0.67 h
Yield: 45.3 %

Procedure:
In a 250 mL flask was placed N-{3-[(2-chloro-4-pyrimidinyl)acetyl]-2-fluorophenyl}-2,6-difluorobenzenesulfonamide (4 g, 9.05 mmol) and DMF (60 mL) was added. NBS (1.62 g, 9.10 mmol) was added and, after stirring at rt for 40 min, 2-methylpropanethioamide (1.4 g, 13.6 mmol), prepared by a procedure analogous to Intermediate 1, was added. After 4 h at rt, the reaction mixture was poured into 800 mL of EtOAc and washed 4 times with 250 mL of H2O, washed once with 200 mL of brine, and dried over NaSO4. Silica gel was added and the volatiles were removed under reduced pressure. Column chromatography with 10% to 60% EtOAc:Hexane gave 2.15 g (45%) of the title compound. 1H-NMR (400 MHz, DMSO-d6) δ 11.43 (s, 1H), 9.06 (d, J=5.3 Hz, 1H), 8.12-8.30 (m, 1H), 7.93-8.06 (m, 2H), 7.84 (t, J=7.9 Hz, 1H), 7.75 (t, J=9.2 Hz, 2H), 7.37 (d, J=5.3 Hz, 1H), 3.77-3.93 (m, 1H), and 1.89 (d, J=6.8 Hz, 6H). MS (ESI): 524 [M]+.
Reaction SMILES: Br[C@H:2]1[C:28](=[O:29])[C@@:27]2([CH3:30])[C@@H:13]([CH2:14][C@@H:15]3[O:20][C@@:19]4([O:26][CH2:25][C@H:23]([CH3:24])[CH2:22][CH2:21]4)[C@@H:17]([CH3:18])[C@@H:16]32)[C@H:12]2[C@H:3]1[C@:4]1([CH3:32])[C@@H:9]([CH2:10][CH2:11]2)[CH2:8][C@@H:7]([OH:31])[CH2:6][CH2:5]1.[OH-:33].[Na+]>O>[CH3:18][C@@H:17]1[C@:19]2([O:26][CH2:25][C@H:23]([CH3:24])[CH2:22][CH2:21]2)[O:20][C@H:15]2[CH2:14][C@@H:13]3[C@@:27]([CH3:30])([C@@H:16]12)[C@H:28]([OH:29])[C:2](=[O:33])[C@H:3]1[C@H:12]3[CH2:11][CH2:10][C@@H:9]2[C@:4]1([CH3:32])[CH2:5][CH2:6][C@H:7]([OH:31])[CH2:8]2
Reactant: [OH-]
Reactant: C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O)CC[C@]5(C)[C@H]4[C@@H](Br)C(=O)[C@]3(C)[C@H]1[C@@H]2C
Agent: [Na+]
Solvent: O
Product: C[C@@H]1CC[C@@]2(OC1)O[C@H]1C[C@H]3[C@@H]4CC[C@H]5C[C@@H](O)CC[C@]5(C)[C@H]4C(=O)[C@@H](O)[C@]3(C)[C@H]1[C@@H]2C
Temperature: 83 °C

Procedure:
A glass lined reactor was charged with 12.4 Kg of (3β,5α,11β,25R)-11-bromospirostan-3-ol-12-one (24.34 mole), 33 gallons of 33 gallons of water and 7.5 Kg (189 mole, 7.75 eq) of sodium hydroxide pellets. The reaction was heated to reflux over 1.5 hours, maintained at reflux for 4.5 hours (pot temperature was 83° C.), then cooled to room temperature. TLC at this point indicated complete reaction.
Reaction SMILES: [CH3:1][C:2]1[N:6]([CH3:7])[C:5]2[CH:8]=[C:9]([C:22]([OH:24])=O)[C:10]3[CH2:11][CH2:12][CH:13]([C:16]4[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=4)[O:14][C:15]=3[C:4]=2[N:3]=1.F[B-](F)(F)F.[N:30]1(OC(N(C)C)=[N+](C)C)[C:34]2C=CC=[CH:38][C:33]=2N=N1.N1CCC1.O>ClCCl>[N:30]1([C:22]([C:9]2[C:10]3[CH2:11][CH2:12][CH:13]([C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=4)[O:14][C:15]=3[C:4]3[N:3]=[C:2]([CH3:1])[N:6]([CH3:7])[C:5]=3[CH:8]=2)=[O:24])[CH2:38][CH2:33][CH2:34]1
Reactant: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Reactant: Cc1nc2c3c(c(C(=O)O)cc2n1C)CCC(c1ccccc1)O3
Agent: C1CNC1
Agent: F[B-](F)(F)F
Solvent: O
Solvent: ClCCl
Product: Cc1nc2c3c(c(C(=O)N4CCC4)cc2n1C)CCC(c1ccccc1)O3
Temperature: 40 °C
Reaction time: 3 h
Yield: 61.1 %

Procedure:
To a suspension of 0.31 g (0.96 mmol) 2,3-dimethyl-8-phenyl-3,6,7,8-tetrahydro-chromeno[7,8-d]imidazole-5-carboxylic acid in dichloromethane (10 ml) were added 0.34 g (1.4 mmol) O-(1H-benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU) and the suspension was heated at 40° C. for 4 h. 102 mg (1.0 mmol) Azetidine were added and the mixture was stirred for 3 h. The reaction mixture was poured into water and the extracted with dichloromethane. The organic layers were dried over magnesium sulphate and concentrated in vacuo. The residue was purified by column chromatography on silica gel (toluene/dioxane=1:5) and crystallized with diisopropyl ether to afford 212 mg (61%) of the title compound as a white solid. m.p. 246°-248° C.
Reaction SMILES: CO.[CH3:3][O:4][C:5](=[O:17])[C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13](=[O:15])[CH3:14])=[CH:8][C:7]=1[OH:16].[CH:18]1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCOC(/N=N/C(OCC)=O)=O>ClCCl>[CH3:3][O:4][C:5](=[O:17])[C:6]1[CH:11]=[CH:10][C:9]([O:12][C:13](=[O:15])[CH3:14])=[CH:8][C:7]=1[O:16][CH3:18]
Reactant: COC(=O)c1ccc(OC(C)=O)cc1O
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CCOC(=O)/N=N/C(=O)OCC
Solvent: CO
Solvent: ClCCl
Product: COC(=O)c1ccc(OC(C)=O)cc1OC
Temperature: 25 °C
Reaction time: 96 h
Yield: 106.7 %

Procedure:
MeOH (0.3 mL, 7.4 mmol) was added to the product from step 1 (0.962 g, 4.6 mmol), Ph3P (1.79 g, 6.8 mmol), and dichloromethane (10 mL). Then DEAD (1.32 mL, 8.4 mmol) was added to the reaction. Reaction was stirred at room temperature for 4 days. Reaction solution was concentrated by rotary evaporation and the resulting residue was purified with silica gel prep plates and 1:3 EtOAc/Hexane as eluent. Obtained 1.10 g of 4-Acetoxy-2-methoxy-benzoic acid methyl ester in quantitative yield.
Reaction SMILES: [Br:1][CH2:2][CH2:3][O:4][C:5]1[C:9]([CH3:10])=[CH:8][S:7][CH:6]=1.C[N:12]1[CH:16]=[CH:15][N:14]=[CH:13]1>>[Br:1][CH2:2][CH2:3][O:4][C:5]1[C:9]([CH3:10])=[CH:8][S:7][CH:6]=1.[NH+:12]1[CH:16]=[CH:15][NH:14][CH:13]=1
Reactant: Cn1ccnc1
Agent: Cc1cscc1OCCBr
Product: c1c[nH+]c[nH]1

Procedure:
Similarly, monomer 2 is prepared from 3-(2-bromoethoxy)-4-methylthiophene (compound 4) and 1-methylimidazole (Aldrich Co.) (see Scheme 2). Compound 4 is prepared according to the procedure developed by Leclerc et al. (Faid, K.; Leclerc, M. J. Chem. Soc., Chem. Commun., 2761, (1996)). The quaternization reaction between 1-methylimidazole and compound 4, provides the desired monomer imidazolium salt 2. (Lucas, P.; Mehdi, N. E.; Ho, H. A.; Belanger, D.; Breau, L. Synthesis, 9, 1253, (2000)).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([CH2:15][CH2:16][C:17]([OH:19])=O)(=[O:14])=[O:13])[CH:6]=[CH:5]2.S(Cl)([Cl:22])=O>CN(C=O)C.C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[C:7]([S:12]([CH2:15][CH2:16][C:17]([Cl:22])=[O:19])(=[O:14])=[O:13])[CH:6]=[CH:5]2
Reactant: O=C(O)CCS(=O)(=O)c1ccc2cc(Cl)ccc2c1
Reactant: O=S(Cl)Cl
Solvent: Cc1ccccc1
Solvent: CN(C)C=O
Product: O=C(Cl)CCS(=O)(=O)c1ccc2cc(Cl)ccc2c1

Procedure:
3-((6-Chloro-2-naphthyl)sulfonyl)propionic acid (14.9 g), thionyl chloride (4.4 mL) and DMF (2 drops) were added to toluene (100 mL), and the mixture was refluxed for 1.5 hours. The solvent was distilled off under reduced pressure, and the residue was washed with ether and hexane to give the title compound (15.5 g) as a brown solid.
Reaction SMILES: [CH2:1]([N:8]1[CH2:18][CH:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[O:16][C:10]2([CH2:15][CH2:14][NH:13][CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH:26]([O:29][C:30]1[CH:38]=[CH:37][C:33]([C:34](O)=[O:35])=[CH:32][C:31]=1[CH3:39])([CH3:28])[CH3:27].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[CH2:1]([N:8]1[CH2:18][CH:17]([C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)[O:16][C:10]2([CH2:15][CH2:14][N:13]([C:34]([C:33]3[CH:37]=[CH:38][C:30]([O:29][CH:26]([CH3:27])[CH3:28])=[C:31]([CH3:39])[CH:32]=3)=[O:35])[CH2:12][CH2:11]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: Clc1ccc(C2CN(Cc3ccccc3)CC3(CCNCC3)O2)cc1
Reactant: Cc1cc(C(=O)O)ccc1OC(C)C
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: Cc1cc(C(=O)N2CCC3(CC2)CN(Cc2ccccc2)CC(c2ccc(Cl)cc2)O3)ccc1OC(C)C
Reaction time: 0.17 h
Yield: 29.5 %

Procedure:
To a solution of 8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecane (100 mg, 0.28 mmol) and 4-isopropoxy-3-methyl-benzoic acid (54 mg, 0.28 mmol) in DMF (1 mL) was added DIEA (98 μL, 0.56 mmol) followed by the addition of HATU (128 mg, 0.34 mmol). The reaction mixture was stirred for 10 minutes, then quenched with water and the aqueous layer was extracted with ethyl acetate. The combined organic layer was washed with water (twice). The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using 0 to 50% EtOAc/hexanes as eluent to obtain [8-benzyl-10-(4-chlorophenyl)-11-oxa-3,8-diazaspiro[5.5]undecan-3-yl]-(4-isopropoxy-3-methyl-phenyl)methanone (44 mg, 29%). ESI-MS m/z calc. 532.2. found 533.3 (M+1)+; Retention time: 2.17 minutes (3 min run).
Reaction SMILES: Br[CH2:2][CH2:3][O:4][C:5]1[CH:12]=[CH:11][C:8]([C:9]#[N:10])=[CH:7][CH:6]=1.[CH:13]12[CH:20]([N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])[CH:17]([CH2:18][CH2:19]1)[CH2:16][NH:15][CH2:14]2.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.C(Cl)Cl>[C:9]([C:8]1[CH:11]=[CH:12][C:5]([O:4][CH2:3][CH2:2][N:15]2[CH2:14][CH:13]3[CH:20]([N:21]([CH3:29])[C:22](=[O:28])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH:17]([CH2:18][CH2:19]3)[CH2:16]2)=[CH:6][CH:7]=1)#[N:10]
Reactant: N#Cc1ccc(OCCBr)cc1
Reactant: CN(C(=O)OC(C)(C)C)C1C2CCC1CNC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: CN(C(=O)OC(C)(C)C)C1C2CCC1CN(CCOc1ccc(C#N)cc1)C2
Yield: 75.1 %

Procedure:
A mixture of 4-(2-bromoethoxy)benzonitrile (see step (i) above; 0.94 g, 4.2 mmol), tert-butyl 3-azabicyclo[3.2.1]oct-8-yl(methyl)carbamate (Preparation D; 0.91 g, 3.8 mmol) and K2CO3 (0.79 g, 5.7 mmol) in 15 mL of dry DMF was stirred at 90° C. overnight before additional K2CO3 (1 g) was added. The mixture was diluted with 300 mL of DCM, and the mixture was washed with water. The organic layer was separated, dried with Na2SO4 and then evaporated. The crude product was purified by flash chromatography on silica gel, eluting with DCM:MeOH (10:1) containing 0.1% TEA, to yield 1.1 g (76%) of the sub-tide compound.
Reaction SMILES: [O:1]=[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:5]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])=[N:4][NH:3]1.[H-].[Na+].[Br:20][C:21]1[CH:28]=[CH:27][C:24]([CH2:25]Br)=[CH:23][C:22]=1[Cl:29].O>CN(C)C=O>[Cl:29][C:22]1[CH:23]=[C:24]([CH:27]=[CH:28][C:21]=1[Br:20])[CH2:25][N:3]1[N:4]=[C:5]([CH2:12][C:13]([O:15][CH2:16][CH3:17])=[O:14])[C:6]2[C:11](=[CH:10][CH:9]=[CH:8][CH:7]=2)[C:2]1=[O:1]
Reactant: Clc1cc(CBr)ccc1Br
Reactant: CCOC(=O)Cc1n[nH]c(=O)c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCOC(=O)Cc1nn(Cc2ccc(Br)c(Cl)c2)c(=O)c2ccccc12
Temperature: 60 °C
Reaction time: 1 h
Yield: 33.8 %

Procedure:
A mixture of ethyl 1,2-dihydro-1-oxophthalazin-4-ylacetate (11.5 g.) and sodium hydride (2.7 g.; 50% w/w dispersion in mineral oil) in dimethylformamide (125 ml.) was stirred at 60° C. for 1 hour under nitrogen. The solution obtained was cooled to room temperature and then 4-bromo-3-chlorobenzyl bromide (15.0 g.) was added, and the mixture stirred at 60° C. for 2 hours. After cooling to 25° C. the reaction mixture was poured into water (500 ml.). The aqueous mixture obtained was extracted with ethyl acetate (400 ml.). The extracts were washed with water, dried (MgSO4), and evaporated to give a solid, which was crystallised from propan-2-ol to yield ethyl 2-(3-chloro-4-bromobenzyl)-1,2-dihydro-1-oxophthalazin-4-ylacetate (7.3 g.), m.p. 142°-145° C.
Reaction SMILES: [CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C@@H:10]2[C:14]3[C:15]([CH3:28])=[C:16]([NH:20][C:21](=[O:27])[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:17]([CH3:19])=[CH:18][C:13]=3[O:12][CH2:11]2)=[CH:6][CH:5]=1)([CH3:3])[CH3:2].[Cl-].[Al+3].[Cl-].[Cl-].[C:33](Cl)(=[O:35])[CH3:34]>ClCCl>[C:33]([C:18]1[C:13]2[O:12][CH2:11][C@H:10]([C:7]3[CH:6]=[CH:5][C:4]([CH:1]([CH3:2])[CH3:3])=[CH:9][CH:8]=3)[C:14]=2[C:15]([CH3:28])=[C:16]([NH:20][C:21](=[O:27])[CH2:22][C:23]([CH3:26])([CH3:25])[CH3:24])[C:17]=1[CH3:19])(=[O:35])[CH3:34]
Reactant: CC(=O)Cl
Reactant: Cc1cc2c(c(C)c1NC(=O)CC(C)(C)C)[C@@H](c1ccc(C(C)C)cc1)CO2
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Product: CC(=O)c1c(C)c(NC(=O)CC(C)(C)C)c(C)c2c1OC[C@@H]2c1ccc(C(C)C)cc1
Temperature: 10 °C
Reaction time: 0.33 h
Yield: 84.2 %

Procedure:
To a solution of (+)-N-((3R)-3-(4-isopropylphenyl)-4,6-dimethyl-2,3-dihydro-1-benzofuran-5-yl)-3,3-dimethylbutanamide (933 mg, 2.46 mmol) obtained in Example 37 in dichloromethane (20 mL) was added aluminum chloride (721 mg, 5.40 mmol) at −70° C. under an argon atmosphere and the mixture was stirred for 20 minutes. To the reaction solution was added dropwise acetyl chloride (424 mg, 5.40 mmol) at the same temperature and the reaction mixture was gradually warmed to 10° C. The reaction solution was added to ice, the organic layer was separated and the aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with water, an aqueous saturated sodium hydrogen carbonate solution and saturated brine, dried over sodium sulfate, filtered, and then concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate 2:1) to synthesize 873 mg (yield: 84%) of the title compound. Melting point: 176-177° C. (ethyl acetate-hexane). [α]D20=+6.2° (c=0.53, chloroform).
Reaction SMILES: [CH:1](=[O:4])[CH2:2][CH3:3].[NH:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.O=O.CN(C1C=CC2N=C3C(=CC(C=C3)=[N+](C)C)SC=2C=1)C>C(Cl)Cl>[CH:1]([N:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1)=[O:4].[CH:1](=[O:4])[CH2:2][CH3:3]
Reactant: C1COCCN1
Agent: CN(C)c1ccc2nc3ccc(=[N+](C)C)cc-3sc2c1
Agent: O=O
Solvent: ClCCl
Solvent: CCC=O
Product: O=CN1CCOCC1

Procedure:
Mixture of propionaldehyde (VII, 2.73 mmole) and morpholine (5.76 mmole) in methylene chloride was irradiated for 90 min with oxygen bubbling in the presence of methylene blue. N-formylmorpholine was obtained in 103% yield on the basis of (VII), as expected. Further, mixture of propionaldehyde (2.73 mmole) and morpholine (11.52 mmole) gave N-formylmorpholine in 145% yield. When n-octylaldehyde (VIII) was used, the yield of N-formylmorpholine went up to 272% by irradiation for 240 min. (Table III.) Also the reaction of mixture of (VIII) and piperidine affords the same results. For example, N-formylpiperidine was obtained in 282% yield for 1.29 mmole of (VIII) and 20.5 mmole of (V). Also, N-formylpiperidine was obtained in 281% yield for the mole ratio of piperidine (V) to n-octylaldehyde (VIII) being 9 for 280 min.
Reaction SMILES: [NH2:1][C:2]1[N+:7]([O-:8])=[C:6]([NH2:9])[CH:5]=[C:4]([N:10]2[CH2:15][CH:14]=[CH:13][CH2:12][CH2:11]2)[N:3]=1.C(Cl)Cl.[CH3:19][O:20][C:21](Cl)=[O:22]>C(N(CC)CC)C>[N:10]1([C:4]2[N:3]=[C:2]([NH:1][C:21]([O:20][CH3:19])=[O:22])[N+:7]([O-:8])=[C:6]([NH:9][C:21]([O:20][CH3:19])=[O:22])[CH:5]=2)[CH2:11][CH:12]=[CH:13][CH2:14][CH2:15]1
Reactant: COC(=O)Cl
Reactant: Nc1cc(N2CC=CCC2)nc(N)[n+]1[O-]
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: COC(=O)Nc1cc(N2CC=CCC2)nc(NC(=O)OC)[n+]1[O-]

Procedure:
45 G. of 2,4-diamino-6-[3,6-dihydro-1(2H)-pyridyl]pyrimidine-3-oxide are mixed in 600 ml. of methylene chloride with 90 ml. of triethylamine and cooled to 5° C. 90 Ml. of chloroformic acid methyl ester are added dropwise while stirring. The mixture is stirred at 5° C. for 30 minutes and at room temperature for 18 hours. Then, the mixture is treated with 100 ml. of methanol and subsequently extracted with 400 ml. of methylene chloride, washed with water, dried over sodium sulfate and evaporated under reduced pressure. Recrystallization of the residue from methanol yields dimethyl 6-[3,6-dihydro-1(2H)-pyridyl]-2,4-pyrimidinedicarbamate-3-oxide having a melting point of 202°-203° C.
Reaction SMILES: [CH2:1]([O:8][C@@H:9]1[C@@H:14]([O:15][CH2:16]C2C=CC=CC=2)[C@H:13]([O:23][CH2:24]C2C=CC=CC=2)[C@@H:12]([CH2:31][O:32][CH2:33]C2C=CC=CC=2)[O:11][C@:10]1([C:41]1[CH:46]=[C:45]([CH2:47][C:48]2[CH:53]=[CH:52][C:51]([CH2:54][CH3:55])=[CH:50][CH:49]=2)[C:44]([Cl:56])=[CH:43][C:42]=1[O:57][CH3:58])O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH2:59]([Si](C)(C)C)[CH:60]=[CH2:61]>>[CH2:59]([C@:10]1([C:41]2[CH:46]=[C:45]([CH2:47][C:48]3[CH:49]=[CH:50][C:51]([CH2:54][CH3:55])=[CH:52][CH:53]=3)[C:44]([Cl:56])=[CH:43][C:42]=2[O:57][CH3:58])[C@H:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[C@@H:14]([O:15][CH2:16][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[C@H:13]([O:23][CH2:24][C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[C@@H:12]([CH2:31][O:32][CH2:33][C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=2)[O:11]1)[CH:60]=[CH2:61]
Reactant: CCc1ccc(Cc2cc([C@]3(O)O[C@H](COCc4ccccc4)[C@@H](OCc4ccccc4)[C@H](OCc4ccccc4)[C@H]3OCc3ccccc3)c(OC)cc2Cl)cc1
Reactant: C=CC[Si](C)(C)C
Product: C=CC[C@@]1(c2cc(Cc3ccc(CC)cc3)c(Cl)cc2OC)O[C@H](COCc2ccccc2)[C@@H](OCc2ccccc2)[C@H](OCc2ccccc2)[C@H]1OCc1ccccc1
Yield: 159.5 %

Procedure:
The title compound (230 mg, 80%) was prepared from 23 (280 mg) and allyltrimethylsilane (167 μL, 120 mg, 3.0 eq.) using the method described for preparing 24.
Reaction SMILES: Cl.[C:2]([NH2:5])(=[NH:4])[CH3:3].C([O:8][CH:9]=[C:10]([C:16](OCC)=O)[C:11]([O:13][CH2:14][CH3:15])=[O:12])C>[O-]CC.[Na+].C(O)C.ClCCl>[CH3:3][C:2]1[NH:4][C:9](=[O:8])[C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:16][N:5]=1
Reactant: CC(=N)N
Reactant: CCOC=C(C(=O)OCC)C(=O)OCC
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Product: CCOC(=O)c1cnc(C)[nH]c1=O
Temperature: 25 °C
Reaction time: 0.08 h
Yield: 26.4 %

Procedure:
Acetamidine hydrochloride (37.16 g, 0.39 mole) was stirred in sodium ethoxide in ethanol (73 mL of a 21% solution, 0.20 mole) for 5 minutes. Diethyl ethoxymethylenemalonate (31.5 mL, 0.15 mole) was added, and the reaction mixture was refluxed for 5 h. The reaction mixture was allowed to cool to room temperature overnight, and diluted with dichloromethane (100 mL). The solution was filtered, washing the solid cake with dichloromethane. The filtrate was concentrated at reduced pressure. The residue was dissolved in dichloromethane (150 mL) and 2.0N HCl (30 mL). The pH of the aqueous layer was 1. The organic layer was washed with water, saturated sodium bicarbonate and brine, dried over anhydrous magnesium sulfate, and the solvent was removed under reduced pressure. The residue was dissolved in hot dichloromethane (50 mL). Ethyl acetate was added (50 mL). The product precipitated. The solution was boiled for 5 minutes, cooled to room temperature, and hexanes were added (50 mL). The resulting crystals were filtered, then washed with ethyl acetate (20 mL) followed by hexanes (50 mL) to yield the title compound (7.22 g, 27%) as off-white crystals. Rf=0.27 (silica gel, 10% isopropanol in dichloromethane).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]3[N:22]([CH3:29])[C:23]([CH3:28])([CH3:27])[C:24](=O)[N:25]=3)[C:9]=2[CH3:30])=[CH:4][CH:3]=1.COC1C=CC(P2(SP(C3C=CC(OC)=CC=3)(=S)S2)=[S:40])=CC=1>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=3[Cl:20])[N:11]=[C:10]([C:21]3[N:22]([CH3:29])[C:23]([CH3:28])([CH3:27])[C:24](=[S:40])[N:25]=3)[C:9]=2[CH3:30])=[CH:4][CH:3]=1
Reactant: COc1ccc(P2(=S)SP(=S)(c3ccc(OC)cc3)S2)cc1
Reactant: Cc1c(C2=NC(=O)C(C)(C)N2C)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Solvent: Cc1ccccc1
Product: Cc1c(C2=NC(=S)C(C)(C)N2C)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(Cl)cc1
Temperature: 60 °C
Yield: 74.2 %

Procedure:
To a solution of compound 6 (98 mg, 0.22 mmol) in toluene (5 mL) was added Lawesson's reagent (150 mg, 0.37 mmol) in one portion. The resulting mixture was heated at 60° C. for 4 h, then poured into ice water. The resulting mixture was extracted with ethyl acetate (2×30 mL). The combined extracts were washed with water, saturated aqueous sodium bicarbonate, and brine, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with hexanes/ethyl acetate (7:3) to give the desired thioketone 21 (78 mg, 77%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 7.48 (d, 1H), 7.32 (d, 2H), 7.28 (dd, 1H), 7.22 (d, 1H), 7.08 (d, 2H), 3.62 (s, 3H), 2.48 (s, 3H), 1.55 (s, 6H); ESMS m/z: 477.0 (M+1).