Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[O-].[Na+].[NH2:4][C:5]1[CH:15]=[CH:14][C:8]([C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:7][CH:6]=1.[CH3:16][C:17](=[CH:19][CH2:20][CH2:21][CH:22](CCO)[CH3:23])[CH3:18].CCO>C1CCCCC1>[NH2:4][C:5]1[CH:6]=[CH:7][C:8]([C:9]([O:11][CH2:12][CH2:13][CH:22]([CH3:23])[CH2:21][CH2:20][CH:19]=[C:17]([CH3:18])[CH3:16])=[O:10])=[CH:14][CH:15]=1
Reactant: CC(C)=CCCC(C)CCO
Reactant: CCOC(=O)c1ccc(N)cc1
Agent: C[O-]
Agent: [Na+]
Solvent: C1CCCCC1
Solvent: CCO
Product: CC(C)=CCCC(C)CCOC(=O)c1ccc(N)cc1
Yield: 30.3 %

Procedure:
Sodium methoxide (2.5 g, cat.) was added to a suspension of ethyl 4-aminobenzoate (10 g, 60 mmol), citronellol (15 g, 90 mmol) in cyclohexane (100 mL). The suspension was heated under reflux for 8 hours with the azeotropic removal of EtOH. The mixture was cooled and filtered through a plug of silica (400 mL) with cyclohexane:isopropanol (95:5) as eluant to give the ester (5.0 g, 30%)as a pale yellow solid.
Reaction SMILES: [CH3:1][C:2]1([CH3:11])[C:7](=[O:8])[O:6][CH2:5][C:4]([CH3:10])([CH3:9])[NH:3]1.Cl.[CH2:13]1[O:15][CH2:14]1>CO>[OH:15][CH2:14][CH2:13][N:3]1[C:4]([CH3:10])([CH3:9])[CH2:5][O:6][C:7](=[O:8])[C:2]1([CH3:11])[CH3:1]
Reactant: C1CO1
Reactant: CC1(C)COC(=O)C(C)(C)N1
Agent: Cl
Solvent: CO
Product: CC1(C)COC(=O)C(C)(C)N1CCO

Procedure:
45.0 g (0.29 moles) of 3,3,5,5-tetramethyl-2-morpholone are dissolved in 450 ml of methanol. The solution is poured into an autoclave, added with 1 ml of concentrated HCl (37%) (% w/w) and pressurized with ethylene oxide (2 bars).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([CH:19]=[CH:20][CH:21]=1)[C:7]([C:9]1[C:14]([C:15]([O:17]C)=O)=[CH:13][CH:12]=[CH:11][N:10]=1)=O)([O-:3])=[O:2].[C:22]1([NH:28][NH2:29])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>C(O)C>[C:22]1([N:28]2[C:15](=[O:17])[C:14]3[CH:13]=[CH:12][CH:11]=[N:10][C:9]=3[C:7]([C:6]3[CH:19]=[CH:20][CH:21]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=3)=[N:29]2)[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: COC(=O)c1cccnc1C(=O)c1cccc([N+](=O)[O-])c1
Reactant: NNc1ccccc1
Solvent: CCO
Product: O=c1c2cccnc2c(-c2cccc([N+](=O)[O-])c2)nn1-c1ccccc1
Yield: 21 %

Procedure:
To a solution of 2-(3-nitrobenzoyl)-3-methoxycarbonylpyridine (0.26 g, 0.97 mmoles) dissolved in ethanol (50 ml), was added phenylhydrazine (0.25 ml, 2.4 mmoles). The mixture was refluxed for 168 hours. The solvent was removed and the solid was precipitated from ethanol and dried, yielding 0.07 g of 6-phenyl-8-(3-nitrophenyl) pyrido[2,3-d]pyridazin-5-one (21%), mp 167° C.
Reaction SMILES: [F:1][C:2]([F:10])([F:9])[C:3]1[N:4]=[C:5]([NH2:8])[S:6][CH:7]=1.[Br:11]N1C(=O)CCC1=O>C(O)(=O)C.C(#N)C.C(Cl)Cl>[Br:11][C:7]1[S:6][C:5]([NH2:8])=[N:4][C:3]=1[C:2]([F:10])([F:9])[F:1]
Reactant: Nc1nc(C(F)(F)F)cs1
Reactant: O=C1CCC(=O)N1Br
Solvent: CC#N
Solvent: CC(=O)O
Solvent: ClCCl
Product: Nc1nc(C(F)(F)F)c(Br)s1
Temperature: 25 °C

Procedure:
To a stirred solution of 4-trifluoromethyl-thiazole-2-ylamine (0.2 g; 1.2 mmol) in acetic acid (0.14 mL) and acetonitrile (1.4 mL) at 0° C. was added N-bromosuccinimide (0.23 g, 1.3 mmol). The reaction mixture was warmed to room temperature over 17 h. The reaction was diluted with methylene chloride, washed with saturated NaHCO3, dried, filtered and concentrated under vacuum to give the crude product. The residue was purified by column chromatography eluting with ethyl acetate/hexanes 0 to 20% to give the product.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:27]([F:30])([F:29])[F:28])[CH2:14][CH2:13][N:12]([C:15]3[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH2:25]O)=[CH:17][N:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8].O1CCCC1.CS(Cl)(=O)=O.O.[NH3:42]>CO>[Cl:1][C:2]1[CH:3]=[C:4]([C:10]2([C:27]([F:30])([F:29])[F:28])[CH2:14][CH2:13][N:12]([C:15]3[N:20]=[C:19]([C:21]([F:24])([F:23])[F:22])[C:18]([CH2:25][NH2:42])=[CH:17][N:16]=3)[CH2:11]2)[CH:5]=[C:6]([Cl:9])[C:7]=1[Cl:8]
Reactant: OCc1cnc(N2CCC(c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)nc1C(F)(F)F
Reactant: N
Agent: CS(=O)(=O)Cl
Solvent: O
Solvent: C1CCOC1
Solvent: CO
Product: NCc1cnc(N2CCC(c3cc(Cl)c(Cl)c(Cl)c3)(C(F)(F)F)C2)nc1C(F)(F)F
Temperature: 25 °C
Reaction time: 1 h
Yield: 45 %

Procedure:
{2-[3-(3,4,5-Trichlorophenyl)-3-(trifluoromethyl)pyrrolidin-1-yl]-4-(tri-fluoromethyl)pyrimidin-5-yl}methanol (1.0 g) was added to tetrahydrofuran (30 mL), and then, under ice cooling, tetrahydrofuran solution (10 mL) comprising methanesulfonyl chloride (0.3 g) was added dropwise thereto. After the dropwise addition was completed, the solution was stirred at room temperature for one hour. The resulting solution was added dropwise to a mixture solution, which was separately prepared to comprise 28% ammonia water (50 mL), tetrahydrofuran (100 mL), and methanol (100 mL), under ice cooling. After the stirring for 12 hours at room temperature, the reaction solution was poured over ice water, and then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate. The solvent was evaporated off under reduced pressure, and the residue was then purified by a silica gel chromatography to obtain the title compound (0.4 g, 45%).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C:10]([CH2:39][CH2:40][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)([CH2:26][CH2:27][O:28][Si](C(C)C)(C(C)C)C(C)C)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:23][CH2:24]3)[C:11](=[O:25])[C:10]([CH2:26][CH2:27][OH:28])([CH2:39][CH2:40][N:41]3[CH2:45][CH2:44][CH2:43][CH2:42]3)[CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)[Si](OCCC1(CCN2CCCC2)C[C@H](c2cccc(Cl)c2)[C@@H](c2ccc(Cl)cc2)N(CC2CC2)C1=O)(C(C)C)C(C)C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: O=C1N(CC2CC2)[C@H](c2ccc(Cl)cc2)[C@@H](c2cccc(Cl)c2)CC1(CCO)CCN1CCCC1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
To an ice-cooled solution of 1.12 g (1.66 mmol) of crude (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-3-(2-(pyrrolidin-1-yl)ethyl)-3-(2-(triisopropylsilyloxy)ethyl)piperidin-2-one (Example 69, Step C, mixture of diastereomers) in THF (55 mL) added 8.3 mL (8.3 mmol) of a 1M solution of TBAF in THF. After being stirred at room temperature for 1.5 h, the reaction mixture was quenched with water and extracted with EtOAc (3×). The combined organic layers were dried (Na2SO4), and concentrated under the reduced pressure. Purification of the residue by flash chromatography on silica gel (3-30% MeOH/DCM, gradient elution) provided the title compound (mixture of C-3 epimers) as a light yellow oil.
Reaction SMILES: [Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([NH:6][C:7](=[O:13])[C:8](=[O:12])[NH:9]2)=[C:4]([N+:14]([O-:16])=[O:15])[C:3]=1F.[CH3:18][O-:19].[Na+]>CS(C)=O.O.Cl>[Cl:1][C:2]1[CH:11]=[C:10]2[C:5]([NH:6][C:7](=[O:13])[C:8](=[O:12])[NH:9]2)=[C:4]([N+:14]([O-:16])=[O:15])[C:3]=1[O:19][CH3:18]
Reactant: C[O-]
Reactant: O=c1[nH]c2cc(Cl)c(F)c([N+](=O)[O-])c2[nH]c1=O
Agent: Cl
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: COc1c(Cl)cc2[nH]c(=O)c(=O)[nH]c2c1[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a stirred solution of 7-Chloro-6-fluoro-5-nitroquinoxaline-2(1H),3(4H)-dione (0.100 g, 0.385 mmol, as prepared above) in DMSO (1.0 mL) at room temperature, sodium methoxide (0.125 g, 2.31 mmol, Mallinckrodt) was added in one portion. The resulting dark red solution was stirred overnight at room temperature. It was then diluted with water (5.0 mL) and acidified with concentrated HCl (6 drops) to pH~2. The precipitated solid was filtered, washed with water (5.0 mL), and dried under vacuum to obtain 0.116 g (110%) of pure (1H NMR) title compound as a yellow powder; m.p. darkens at 316° C.; 1H NMR (DMSO-d6): δ 3.821 (s, 3H), 7.275 (s, 1H), 12.079 (s, 1H) 12.121 (s, 1H). The NMR also indicates the presence. of DMSO (reaction solvent).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[N:17]=[C:16]([N:18]3[CH2:23][C@H:22]([CH3:24])[N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:20]([CH3:32])[CH2:19]3)[CH:15]=[CH:14][C:13]=2[O:33][CH3:34])(=[O:10])=[O:9])=[C:4]([Cl:35])[CH:3]=1.[O:36]1[CH:40]=[CH:39][C:38](B2OC(C)(C)C(C)(C)O2)=[CH:37]1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.C(OCC)(=O)C>[Cl:35][C:4]1[CH:3]=[C:2]([C:38]2[CH:39]=[CH:40][O:36][CH:37]=2)[CH:7]=[CH:6][C:5]=1[S:8]([NH:11][C:12]1[N:17]=[C:16]([N:18]2[CH2:23][C@H:22]([CH3:24])[N:21]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:20]([CH3:32])[CH2:19]2)[CH:15]=[CH:14][C:13]=1[O:33][CH3:34])(=[O:10])=[O:9]
Reactant: COc1ccc(N2C[C@@H](C)N(C(=O)OC(C)(C)C)[C@@H](C)C2)nc1NS(=O)(=O)c1ccc(Br)cc1Cl
Reactant: CC1(C)OB(c2ccoc2)OC1(C)C
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Solvent: CCOC(C)=O
Product: COc1ccc(N2C[C@@H](C)N(C(=O)OC(C)(C)C)[C@@H](C)C2)nc1NS(=O)(=O)c1ccc(-c2ccoc2)cc1Cl
Yield: 116 %

Procedure:
1,1-Dimethylethyl (2R,6S)-4-[6-{[(4-bromo-2-chlorophenyl)sulfonyl]amino}-5-(methyloxy)-2-pyridinyl]-2,6-dimethyl-1-piperazinecarboxylate (D13) (0.15 g, 0.254 mmol), 2-(3-furanyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (0.0739 g, 0.381 mmol), Palladium dichloride di-triphenylphosphine (9.0 mg, 0.0127 mmol), sodium carbonate (0.053 g, 0.508 mmol) were heated in DME (2 mL) and water (1 mL) at 120° C. in the microwave for 20 minutes. The reaction was then diluted with ethyl acetate (50 mL) and washed with saturated sodium hydrogen carbonate (2×30 mL) and brine (30 mL). The organic layer was dried (MgSO4) and evaporated to give a yellow oil which was purified by chromatography [silica gel, eluting with 0 to 60% Ethyl acetate/pentane]. Product fractions evaporated to give a pale yellow foam (D15) (0.170 g) MS (ES+) m/e 577/579 [M+H]+.
Reaction SMILES: [C@@H:1]12[C:10](=[O:11])[O:9][C:7](=O)[C@@H:2]1[CH2:3][CH:4]=[CH:5][CH2:6]2.[NH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][N:20]([C:23]2[N:28]=[CH:27][CH:26]=[CH:25][N:24]=2)[CH2:19][CH2:18]1.C(O)CCC.[ClH:34]>C(O)(C)C>[ClH:34].[N:24]1[CH:25]=[CH:26][CH:27]=[N:28][C:23]=1[N:20]1[CH2:21][CH2:22][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][N:12]2[C:10](=[O:11])[CH:1]3[CH2:6][CH:5]=[CH:4][CH2:3][CH:2]3[C:7]2=[O:9])[CH2:18][CH2:19]1
Reactant: NCCCCN1CCN(c2ncccn2)CC1
Reactant: O=C1OC(=O)[C@@H]2CC=CC[C@H]12
Agent: Cl
Solvent: CCCCO
Solvent: CC(C)O
Product: O=C1C2CC=CCC2C(=O)N1CCCCN1CCN(c2ncccn2)CC1

Procedure:
A mixture of cis-4-cyclohexene-1,2-dicarboxylic anhydride (633 mg; 4.25 mmol), 1-(4-aminobutyl)-4-(2-pyrimidinyl)piperazine (1 g; 4.25 mmol) and n-butanol (10 ml) was heated under reflux for 6 hours. The solvent was removed under reduced pressure, and the residue was purified by silica gel chromatography to give an oily substance. The oily substance was treated with a mixture of 3% hydrogen chloride in isopropanol, and the precipitate was recrystallized from isopropanol to give N-[4-{4-(2-pyrimidinyl)-1-piperazinyl}butyl]-4-cyclohexene-1,2-dicarboximide hydrochloride. M.P., 177°-179° C.
Reaction SMILES: [C:1]12([C:11]3[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17](O)=[O:18])=[CH:13][CH:12]=3)[CH2:10][CH:5]3[CH2:6][CH:7]([CH2:9][CH:3]([CH2:4]3)[CH2:2]1)[CH2:8]2.[NH2:22][C:23]1[CH:24]=[N:25][CH:26]=[C:27]([CH:31]=1)[C:28]([NH2:30])=[O:29].C1CN([P+](ON2N=NC3C=CC=CC2=3)(N2CCCC2)N2CCCC2)CC1.F[P-](F)(F)(F)(F)F.CO>CN(C1C=CN=CC=1)C.CN(C=O)C>[C:1]12([C:11]3[CH:21]=[CH:20][C:14]([O:15][CH2:16][C:17]([NH:22][C:23]4[CH:24]=[N:25][CH:26]=[C:27]([CH:31]=4)[C:28]([NH2:30])=[O:29])=[O:18])=[CH:13][CH:12]=3)[CH2:2][CH:3]3[CH2:9][CH:7]([CH2:6][CH:5]([CH2:4]3)[CH2:10]1)[CH2:8]2
Reactant: NC(=O)c1cncc(N)c1
Reactant: O=C(O)COc1ccc(C23CC4CC(CC(C4)C2)C3)cc1
Agent: CN(C)c1ccncc1
Agent: F[P-](F)(F)(F)(F)F
Agent: c1ccc2c(c1)nnn2O[P+](N1CCCC1)(N1CCCC1)N1CCCC1
Solvent: CN(C)C=O
Solvent: CO
Product: NC(=O)c1cncc(NC(=O)COc2ccc(C34CC5CC(CC(C5)C3)C4)cc2)c1
Temperature: 25 °C
Yield: 61.6 %

Procedure:
To solution of (4-adamantan-1-yl-phenoxy)-acetic acid (50 mg, 0.17 mmol), 5-amino nicotinamide (47.89 mg, 0.34 mmol) and DMAP (42.71 mg, 0.34 mmol) in DMF 5 ml was added PyBOP (181 mg, 0.34 mmol), and stirred room temperature. Reaction mixture was poured onto ice cold water, diluted by methanol/MC mixture (10%). The organic phase was separated, sequentially washed with aqueous sodium bicarbonate, brine and water, dried over anhydrous MgSO4, and concentrated. The residue was purified by preparative-TLC(CH2Cl2:MeOH=6:1) to afford 5-[2-(4-adamantan-1-yl-phenoxy)-acetylamino]-nicotinamide as a colorless solid (42.48 mg, 60% yield).
Reaction SMILES: [F:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].S(=O)(=O)(O)O.[CH3:17][CH2:18]O>>[F:1][C:2]1[C:10]([CH3:11])=[CH:9][CH:8]=[CH:7][C:3]=1[C:4]([O:6][CH2:17][CH3:18])=[O:5]
Reactant: Cc1cccc(C(=O)O)c1F
Reactant: CCO
Agent: O=S(=O)(O)O
Product: CCOC(=O)c1cccc(C)c1F
Temperature: 90 °C
Reaction time: 8 h

Procedure:
2-Fluoro-3-methylbenzoic acid (8.0 g) was mixed with EtOH (100 ml), and concentrated sulfuric acid was added thereto, followed by stirring at 90° C. overnight. The reaction mixture was concentrated under reduced pressure, and EtOAc and water were then added thereto. The organic layer was washed with a saturated aqueous sodium hydrogen carbonate solution, then dried over Na2SO4, and concentrated under reduced pressure to obtain ethyl 2-fluoro-3-methylbenzoate (7.84 g).
Reaction SMILES: [CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[CH:5][C:4]([C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)=[N:3]1.[Br:14]N1C(=O)CCC1=O>C(#N)C.[O-2].[O-2].[Mn+4]>[Br:14][C:5]1[C:4]([C:9]2[CH:13]=[CH:12][S:11][CH:10]=2)=[N:3][N:2]([CH3:1])[C:6]=1[CH:7]=[O:8]
Reactant: Cn1nc(-c2ccsc2)cc1CO
Reactant: O=C1CCC(=O)N1Br
Agent: [Mn+4]
Agent: [O-2]
Solvent: CC#N
Product: Cn1nc(-c2ccsc2)c(Br)c1C=O
Temperature: 25 °C
Reaction time: 24 h
Yield: 83.3 %

Procedure:
A solution of [1-methyl-3-(thiophen-3-yl)-1H-pyrazol-5-yl]methanol (4b) (271 mg, 1.39 mmol) and N-bromosuccinimide (236 mg, 1.32 mmol) in acetonitrile (23 mL) was stirred at room temperature for 1 hour. The reaction mixture was concentrated in vacuo. Water (10 mL) was added and the aqueous layer was extracted with ethyl acetate (2×12 mL). The organic layer was dried over sodium sulfate and concentrated in vacuo. The residue was taken in dichloromethane (5 mL) and manganese dioxide (1.21 g, 13.95 mmol) was added. The reaction mixture was stirred at room temperature for 24 hours, filtered over Celite®, and the filtrate was concentrated in vacuo. to provide 4-bromo-1-methyl-3-(thiophen-3-yl)-1H-pyrazole-5-carbaldehyde (4c) (297 mg, 1.10 mmol, 78%), which was used without further purification.
Reaction SMILES: [N:1]1([C:7]2[N:12]=[C:11]([NH:13][C:14](OCC)=[O:15])[N+:10]([O-:19])=[C:9]([NH:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:8]=2)[CH2:6][CH:5]=[CH:4][CH2:3][CH2:2]1>CN(C)C=O>[N:1]1([C:7]2[N:8]=[C:9]([NH:20][C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:10]3[O:19][C:14](=[O:15])[N:13]=[C:11]3[N:12]=2)[CH2:6][CH:5]=[CH:4][CH2:3][CH2:2]1
Reactant: CCOC(=O)Nc1nc(N2CC=CCC2)nc(NC(=O)OCC)[n+]1[O-]
Solvent: CN(C)C=O
Product: CCOC(=O)Nc1nc(N2CC=CCC2)nc2nc(=O)on12

Procedure:
4.8 g. of diethyl 6-[3,6-dihydro-1(2H)-pyridyl]-s-triazin-2,4-dicarbamate-3-oxide are mixed with 100 ml. of absolute dimethylformamide and stirred at 140° C. for 30 minutes. The solvent is then evaporated off under reduced pressure and the residue is recrystallized from methylene chloride and diethyl ether, there being obtained pure ethyl 5-[3,6-dihydro-1(2H)-pyridyl]-2-oxo-2H-[1,2,4]oxadiazolo[2,3-a]-s-triazine-7-carbamate having a melting point of 220°-225° C. (decomposition).
Reaction SMILES: [C:1]([O:7][CH2:8][CH3:9])(=[O:6])[CH2:2][C:3]([CH3:5])=[O:4].C(=O)([O-])[O-].[K+].[K+].[C:16](=S)=[S:17].CI.[CH3:21][S:22]([CH3:24])=O>>[C:3]([C:2](=[C:21]([S:17][CH3:16])[S:22][CH3:24])[C:1]([O:7][CH2:8][CH3:9])=[O:6])(=[O:4])[CH3:5]
Reactant: S=C=S
Reactant: CCOC(=O)CC(C)=O
Reactant: CS(C)=O
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CI
Product: CCOC(=O)C(C(C)=O)=C(SC)SC
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
In 100 ml of dimethyl sulfoxide is dissolved 50.0 g of ethyl acetoacetate. To the solution is added at room temperature 53.1 g of potassium carbonate, and the mixture is stirred for 30 minutes. To the resultant is added, while keeping the inner temperature at 10° C., 29.3 g of carbon disulfide dropwise over a period of 30 minutes, followed by stirring at 10° C. for one hour. To the mixture is further added 120.0g of methyl iodide dropwise at the same temperature over a period of 30 minutes, which is stirred at the same temperature for one hour. The inner temperature is reverted to room temperature, then the reaction mixture is stirred for one hour, poured into 200 ml of ice water, and extracted with dichloromethane. The extract is washed with water, dried and concentrated to give 66.0 g of the title compound as a light brown oil.
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1[C:7](Cl)=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2].[CH2:15]([N:17](CC)CC)C.CN>O1CCCC1.CCCCCC>[CH2:1]([O:3][C:4]([C:6]1[C:7]([NH:17][CH3:15])=[N:8][C:9]([S:12][CH3:13])=[N:10][CH:11]=1)=[O:5])[CH3:2]
Reactant: CCN(CC)CC
Reactant: CCOC(=O)c1cnc(SC)nc1Cl
Agent: CN
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CCOC(=O)c1cnc(SC)nc1NC
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 80.4 %

Procedure:
To a solution of 4-chloro-2-methylsulfanyl-5-pyrimidinecarboxylate ethyl ester (18.66 g, 80.4 mmol) in 260 mL of tetrahydrofuran was added triethylamine (34 mL, 244 mmol), followed by 30 mL of a 40% aqueous solution of methylamine. The solution was stirred for 30 minutes at 25° C. then concentrated in vacuo and partitioned between chloroform and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over MgSO4, filtered, and concentrated to provide a white solid. The solid was suspended in hexane and filtered to provide 14.70 g (81%) of 4-methylamino-2-methylsulfanyl-5-pyrimidinecarboxylate ethyl ester; mp 91°-93° C.
Reaction SMILES: [F:1][C:2]1[C:3]([N:11]2[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13][CH2:12]2)=[N:4][CH:5]=[C:6](/[CH:8]=[CH:9]/[CH3:10])[CH:7]=1.CS(N)(=O)=[O:26].CC[C@H]1[C@H]2C[C@H]([C@H](OC3C4C(=CC=CC=4)C(O[C@H](C4C=CN=C5C=4C=C(OC)C=C5)[C@@H]4N5C[C@H](CC)[C@@H](CC5)C4)=NN=3)C3C=CN=C4C=3C=C(OC)C=C4)N(CC2)C1.S([O-])([O-])=O.[Na+].[Na+].[OH2:93]>C(O)(C)(C)C.CCOC(C)=O>[OH:93][C@@H:8]([C:6]1[CH:7]=[C:2]([F:1])[C:3]([N:11]2[CH2:12][CH2:13][N:14]([C:17]([O:19][C:20]([CH3:22])([CH3:21])[CH3:23])=[O:18])[CH2:15][CH2:16]2)=[N:4][CH:5]=1)[C@@H:9]([OH:26])[CH3:10]
Reactant: O
Reactant: C/C=C/c1cnc(N2CCN(C(=O)OC(C)(C)C)CC2)c(F)c1
Reactant: CS(N)(=O)=O
Agent: CC[C@@H]1CN2CC[C@@H]1C[C@@H]2[C@H](Oc1nnc(O[C@H](c2ccnc3ccc(OC)cc23)[C@H]2C[C@@H]3CCN2C[C@@H]3CC)c2ccccc12)c1ccnc2ccc(OC)cc12
Agent: O=S([O-])[O-]
Agent: [Na+]
Solvent: CCOC(C)=O
Solvent: CC(C)(C)O
Product: C[C@H](O)[C@@H](O)c1cnc(N2CCN(C(=O)OC(C)(C)C)CC2)c(F)c1
Temperature: 5 °C
Reaction time: 16 h
Yield: 99 %

Procedure:
To a solution of 105 (2.67 g, 8.29 mmol) in tert-butanol (80 mL) and water (80 mL) was added methanesulfonamide (0.79 g, 8.29 mmol, Sigma-Aldrich). The mixture was cooled to 5° C. and AD-mix-α (11.50 g, 8.29 mmol) was added to form a reaction mixture. After warming the reaction mixture to a temperature of about 25° C. and stirring for 16 hours, excess solid sodium sulfite was added and the resulting slurry was allowed to stir at 15° C. for 30 min. The mixture was extracted twice with EtOAc. The organic portions were combined, washed with brine, dried (Na2SO4), and concentrated under reduced pressure. The residue was chromatographed on a silica gel column eluted with 50:50 EtOAc:hexanes and 70:30 EtOAc:hexanes to provide 106 as a solid (>99% yield).
Reaction SMILES: Cl[Si]1(Cl)CCC1.Cl[Si:8]1([CH3:12])[CH2:11][CH2:10][CH2:9]1.[C:13]([O:16]C(=O)C)(=[O:15])[CH3:14]>CO>[C:13]([O:16][Si:8]1([CH3:12])[CH2:11][CH2:10][CH2:9]1)(=[O:15])[CH3:14]
Reactant: CC(=O)OC(C)=O
Reactant: C[Si]1(Cl)CCC1
Agent: Cl[Si]1(Cl)CCC1
Solvent: CO
Product: CC(=O)O[Si]1(C)CCC1

Procedure:
Several silacyclobutane monomers are known. For example, see U.S. Pat. No. 3,046,291 to Leo H. Sommer, and U.S. Pat. No. 3,687,995 to David Jonas et al. Sommer prepared his silacyclobutanes by reacting ClCH2CHRCH2SiR'Cl2 with magnesium. Jonas et al. teach organosilicon compounds having the general formula ##STR4## where R represents an atom or radical selected from the group consisting of hydrogen atom and alkyl radicals having less than 7 carbon atoms and R' represents alkoxy radicals having less than 5 carbon atoms or a radical of the formula --NR"2, in which each R" is a hydrogen atom or an alkyl radical. In U.S. Pat. No. 3,694,427, issued Sept. 26, 1972, Jonas et al. teach that R' can also be acyloxy radical. As an example, the reaction of 1,1-dichlorosilacyclobutane with methylorthoformate gave 1,1-dimethoxysilacyclobutane ##STR5## in 78% yield. Further, the same compound was prepared in only 59% yield by reaction of 1,1-dichlorosilacyclobutane and methanol (Bush, R. Ph.D. Thesis, Univ. of California at Davis, 1975; Diss. Abstr. Int. B 1976, 36, 5034). Similarly, the reaction of 1-chloro-1-methyl-silacyclobutane and acetic anhydride gave 1-acetoxy-1-methyl-silacyclobutane ##STR6## in 48% yield (Nametkin, N. S.; Vdovin, V. M.; Grinberg, P. L. Dokl. Akad. Nauk SSSR, 1964, 155, 849 [320]) Silacyclobutane silazanes have been prepared by metathesis reaction with formation of alkali metal salt or condensation reaction with formation of HCl (Nametkin, N. S.; Vdovin, V. M.; Babich, E. D.; Oppengeim, V. D. Khim. Geterotsikl. Soedin., 1965, 455) and British Patent No. 1,328,514 to Bush et al. These reactions generally give less than quantitative yields and require additional processing steps in comparison to the invention process. The invention process also provides novel compounds. See also Nametkin, N. S.; Vdovin, J. M.; Babich, E. D. Khim. Geterotsikl. Soedin., 1967, 148. Transsilylation of silazanes is taught and transsilylation of 1-chloro-1-methylsilacyclobutane with disilazanes is shown.