Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(OP([CH2:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:12][CH:11]=1)(OCC)=O)C.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:30][C:31]1([CH3:49])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])[CH:42]=O)[CH:39]=2)[S:34][CH2:33][CH2:32]1>C1COCC1.CCCCCC>[CH3:49][C:31]1([CH3:30])[C:40]2[C:35](=[CH:36][CH:37]=[C:38]([CH:41]([CH2:44][CH2:45][CH2:46][CH2:47][CH3:48])/[CH:42]=[CH:9]/[C:10]3[CH:11]=[CH:12][C:13]([C:14]([O:16][CH3:17])=[O:15])=[CH:18][CH:19]=3)[CH:39]=2)[S:34][CH2:33][CH2:32]1
Reactant: CCOP(=O)(Cc1ccc(C(=O)OC)cc1)OCC
Reactant: CCCCCC(C=O)c1ccc2c(c1)C(C)(C)CCS2
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CCCCCC(/C=C/c1ccc(C(=O)OC)cc1)c1ccc2c(c1)C(C)(C)CCS2
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 39.3 %

Procedure:
0.51 g of methyl 4-(diethoxyphosphorylmethyl)-benzoate were dissolved in 7.5 ml THF and treated, at −20° C., with 1.8 ml of a 1M solution of lithium bis(trimethylsilyl)amide in hexane. After 15 min. at −20° C., a solution of 350 mg of (RS)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanal in 7.5 ml THF was added. The reaction mixture was stirred at room temperature for 1.5 hour. The mixture quenched by the addition of 10 ml of water and the resulting mixture was partitioned in 25 ml ethyl acetate/15 ml sat. aq. sodium chloride solution. The phases were separated and the organic phase was dried over MgSO4. The solvent was removed in vacuo and the crude product was purified by flash chromatography (SiO2, 10% ethyl acetate/hexanes), giving 200 mg of the corresponding ester. 1H NMR (CDCl3): 7.94 (d, J=8.5 Hz, 2H), 7.38 (d, J=8.5 Hz, 2H), 7.19 (d, J=1.8 Hz, 1H), 7.03 (d, J=8.1 Hz, 1H), 6.91 (dd, J=8.1, 1.8 Hz, 1H), 6.45 (d, J=15.9 Hz, 1H), 6.38 (d, J=15.9 Hz, 1H), 3.90 (s, 3H), 3.30 (m, 1H), 3.05-3.00 (m, 2H), 2.00-1.90 (m, 2H), 1.85-1.75 (m, 2H), 1.33 (s, 6H), 1.40-1.30 (m, 6H), 0.86 (t, J=6.5 HZ, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:9]=[CH:8][C:6]([NH2:7])=[CH:5][C:4]=1[F:10].Cl[C:12](OC1C=CC([N+]([O-])=O)=CC=1)=[O:13].C(N(C(C)C)CC)(C)C.[Cl:33][C:34]1[CH:43]=[C:42]2[C:37]([C:38]([N:44]3[CH2:49][CH2:48][NH:47][CH2:46][CH2:45]3)=[CH:39][CH:40]=[N:41]2)=[CH:36][CH:35]=1>>[Cl:33][C:34]1[CH:43]=[C:42]2[C:37]([C:38]([N:44]3[CH2:49][CH2:48][N:47]([C:12]([NH:7][C:6]4[CH:8]=[CH:9][C:3]([O:2][CH3:1])=[C:4]([F:10])[CH:5]=4)=[O:13])[CH2:46][CH2:45]3)=[CH:39][CH:40]=[N:41]2)=[CH:36][CH:35]=1
Reactant: Clc1ccc2c(N3CCNCC3)ccnc2c1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: COc1ccc(N)cc1F
Solvent: CCN(C(C)C)C(C)C
Product: COc1ccc(NC(=O)N2CCN(c3ccnc4cc(Cl)ccc34)CC2)cc1F

Procedure:
As described for example 78, 4-methoxy-3-fluoro-aniline, p-nitrophenyl chloroformate, diisopropylethyl amine, and 7-chloro-4-piperazinylquinoline are reacted to afford the product. LC-MS: 415 (M++1). 1H NMR (CDCl3) δ 8.78 (d, 1H), 8.05 (s, 1H), 7.95 (d, 1H), 7.50 (d, 1H), 7.35 (d, 1H), 7.00 (m, 1H), 6.85 (d, 1H), 6.70 (m, 1H), 6.60 (s, 1H), 3.85 (s, 3H), 3.78 (m, 4H), 3.25 (m, 4H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[F:10])[CH2:5][OH:6].[H-].[Na+].[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18](F)[C:15]=1[C:16]#[N:17]>CN(C)C=O>[F:13][C:14]1[CH:21]=[CH:20][CH:19]=[C:18]([O:6][CH2:5][C:4]2[CH:7]=[CH:8][C:9]([F:10])=[C:2]([F:1])[CH:3]=2)[C:15]=1[C:16]#[N:17]
Reactant: OCc1ccc(F)c(F)c1
Reactant: N#Cc1c(F)cccc1F
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#Cc1c(F)cccc1OCc1ccc(F)c(F)c1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
3,4-Difluorobenzyl alcohol (1.47 g; 10.1 mmol) was added to a cooled (0° C.) slurry of sodium hydride (0.414 g; 10.3 mmol) in dimethylformamide under nitrogen atmosphere. The reaction mixture was slowly warmed to room temperature, stirred for 1 hour. The reaction mixture was then added to a cooled (0° C.) solution of 2,6-difluorobenzonitrile in dimethylformamide, stirred for 3 hours at room temperature. The reaction mixture was poured on crushed ice-water, stirred, filtered, washed with water and dried to afford 1.47 grams of 2-fluoro-6-(3,4-diflurophenylmethoxy)benzonitrile.
Reaction SMILES: Br[CH:2]([CH3:13])[C:3]([C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][CH:6]=1)=O.[NH2:14][C:15]([NH2:17])=[S:16]>CCO>[CH3:12][O:11][C:8]1[CH:9]=[CH:10][C:5]([C:3]2[N:14]=[C:15]([NH2:17])[S:16][C:2]=2[CH3:13])=[CH:6][CH:7]=1
Reactant: NC(N)=S
Reactant: COc1ccc(C(=O)C(C)Br)cc1
Solvent: CCO
Product: COc1ccc(-c2nc(N)sc2C)cc1
Yield: 77.5 %

Procedure:
A mixture of 2-bromo-1-(4-methoxyphenyl)propan-1-one (10.4 g, 36.1 mmol) and thiourea (2.76 g, 36.2 mmol) in 95% EtOH (70 mL) was heated at reflux for 60 min. The solution was concentrated and mixed with water (100 mL) and saturated aqueous Na2CO3 (5.0 mL). The resultant precipitate was filtered and recrystallized in toluene. The solids were filtered and dried under vacuum to give 4-(4-methoxyphenyl)-5-methylthiazol-2-amine (6.16 g) as yellow solids in 78% yield: 1H NMR (500 MHz, DMSO-d5) δ 8.90 (s, 2H), 7.46-7.44 (m, 2H), 7.09-7.07 (m, 2H), 3.81 (s, 3H), 2.47 (s, 3H).
Reaction SMILES: [CH2:1]([O:5][C:6]1[CH:31]=[C:30]([O:32][CH2:33][CH:34]([CH3:36])[CH3:35])[CH:29]=[CH:28][C:7]=1[C:8]([C:10]1[CH:11]=[CH:12][C:13]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[C:14]([CH:22]=1)[O:15][CH2:16][C:17]([O:19]CC)=[O:18])=[O:9])[CH:2]([CH3:4])[CH3:3].[OH-].[Na+].O.Cl>C(O)C.C(Cl)(Cl)Cl>[CH2:1]([O:5][C:6]1[CH:31]=[C:30]([O:32][CH2:33][CH:34]([CH3:36])[CH3:35])[CH:29]=[CH:28][C:7]=1[C:8]([C:10]1[CH:11]=[CH:12][C:13]([O:23][CH2:24][CH:25]([CH3:27])[CH3:26])=[C:14]([CH:22]=1)[O:15][CH2:16][C:17]([OH:19])=[O:18])=[O:9])[CH:2]([CH3:4])[CH3:3]
Reactant: CCOC(=O)COc1cc(C(=O)c2ccc(OCC(C)C)cc2OCC(C)C)ccc1OCC(C)C
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: ClC(Cl)Cl
Solvent: CCO
Solvent: O
Product: CC(C)COc1ccc(C(=O)c2ccc(OCC(C)C)c(OCC(=O)O)c2)c(OCC(C)C)c1
Temperature: 25 °C
Reaction time: 1 h
Yield: 92.6 %

Procedure:
In 10 ml of ethanol is dissolved 0.95 g of ethyl 2-[5-(2,4-diisobutoxybenzoyl)-2-isobutoxyphenoxy]acetate, to which is added 5.7 ml of 1 mol/L solution of sodium hydroxide. The mixture thus obtained is stirred at ambient temperature for one hour. Water and chloroform are added to the reaction mixture, pH is adjusted to 2 with 6 mol/L hydrochloric acid, and the organic layer is separated. The organic layer is washed with water and saturated aqueous solution of sodium chloride successively and dried on anhydrous magnesium sulfate, and the solvent is distilled off under reduced pressure. Thus, 0.83 g of 2-[5-(2,4-diisobutoxybenzoyl)-2-isobutoxyphenoxy]acetic acid is obtained as a white solid product.
Reaction SMILES: [F:1][C:2](=[CH2:6])[C:3](Cl)=[O:4].[Cl:7][C:8]1[CH:9]=[C:10]([CH:13]=[C:14]([Cl:17])[C:15]=1[OH:16])[C:11]#[N:12].C(N(CC)CC)C>C(Cl)Cl>[F:1][C:2](=[CH2:6])[C:3]([O:16][C:15]1[C:14]([Cl:17])=[CH:13][C:10]([C:11]#[N:12])=[CH:9][C:8]=1[Cl:7])=[O:4]
Reactant: N#Cc1cc(Cl)c(O)c(Cl)c1
Reactant: C=C(F)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: C=C(F)C(=O)Oc1c(Cl)cc(C#N)cc1Cl
Reaction time: 0.5 h
Yield: 80.8 %

Procedure:
10 g (0.092 mol) of α-fluoroacryloyl chloride (obtained in accordance with example 1c) were added dropwise, at a temperature of 5° C., with stirring and in the course of 20 minutes, to a solution of 16.7 g (0.089 mol) of 3,5-dichloro-4-hydroxybenzonitrile and 9 g (0.089 mol) of triethylamine in 200 ml of anhydrous methylene dichloride, and the reaction mixture was then stirred for a further 30 minutes at the same temperature. The solid formed was filtered off and washed with 20 ml of anhydrous methylene dichloride. After 0.005 g of hydroquinone monomethyl ether had been added, the volatile constituents in the mixture of filtrate and wash solution were removed by distillation, and the residue was recrystallized from boiling n-heptane. 18.7 g (81% of theory) of 2,6-dichloro-4-cyanophenyl α-fluoroacrylate were obtained, melting point 95° to 99° C.
Reaction SMILES: Cl[S:2]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][C:10](=[O:15])[C:9]3[NH:16][CH:17]=[C:18]([C:19]([OH:21])=[O:20])[C:8]=3[C:7]=2[CH:6]=1)(=[O:4])=[O:3].[CH3:22][N:23]([CH3:28])[CH2:24][CH2:25][CH2:26][NH2:27]>>[CH3:22][N:23]([CH3:28])[CH2:24][CH2:25][CH2:26][NH:27][S:2]([C:5]1[CH:14]=[CH:13][C:12]2[NH:11][C:10](=[O:15])[C:9]3[NH:16][CH:17]=[CH:18][C:8]=3[C:7]=2[CH:6]=1)(=[O:3])=[O:4].[CH2:18]([C:19]([O-:21])=[O:20])[CH3:17]
Reactant: CN(C)CCCN
Reactant: O=C(O)c1c[nH]c2c(=O)[nH]c3ccc(S(=O)(=O)Cl)cc3c12
Product: CCC(=O)[O-]
Product: CN(C)CCCNS(=O)(=O)c1ccc2[nH]c(=O)c3[nH]ccc3c2c1
Yield: 20.3 %

Procedure:
This compound is prepared according to synthesis 25, from 115 mg (0.35 mmol) of 8-chlorosulfonyl-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-carboxylic acid (synthesis 2) and 53 μL (0.42 mmol) of 3-dimethylaminopropylamine. After purification by chromatography on silica (eluent chloroform/methanol/ammonia 160/25/4), 15 mg (10%) of 8-(3-dimethylamino-propylsulfamoyl)-4-oxo-4,5-dihydro-3H-pyrrolo[2,3-c]quinoline-1-ethyl carboxylate is obtained in the form of a white solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH3:12])[CH:6]=[CH:7][C:8]=1[C:9](O)=O.[BH4-].[Na+].[B].C([O:19]C(C)C)(C)C>O1CCCC1.O>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:6]=[CH:7][C:8]=1[CH3:9])[CH2:12][OH:19]
Reactant: CC(C)OC(C)C
Reactant: COc1cc(C)ccc1C(=O)O
Agent: [BH4-]
Agent: [B]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: COc1cc(CO)ccc1C
Reaction time: 0.17 h

Procedure:
A solution of 3-methoxy-p-toluic acid (45.32 g) in tetrahydrofuran (280 ml) was added to a suspension of sodium borohydride (9.29 g) in tetrahydrofuran (45 ml) with ice bath cooling under nitrogen atmosphere. After 10 minutes stirring, boron trifuluoride diethyl etherate (41.5 ml) was added to the mixture at 3 to 15° C. and the whole was stirred at room temperature overnight. Water (210 ml) and diisopropyl ether (60 ml) were added to the mixture. The organic layer was separated and the aqueous layer was extracted with diisopropyl ether (100 ml). The combined organic layer was washed successively with 1N sodium hydroxide solution and brine, dried over sodium sulfate, and evaporated in vacuo to give 3-methoxy-4-methylbenzylalcohol (41.63 g) as an oil.
Reaction SMILES: [OH:1][C@@H:2]([CH3:10])[C:3]([N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:4].C(N(CC)CC)C.[Br:18][CH:19]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:20](Cl)=[O:21]>ClCCCl.O>[Br:18][CH:19]([C:23]1[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=1)[C:20]([O:1][C@@H:2]([CH3:10])[C:3](=[O:4])[N:5]1[CH2:9][CH2:8][CH2:7][CH2:6]1)=[O:21]
Reactant: O=C(Cl)C(Br)c1ccc(Cl)cc1
Reactant: C[C@H](O)C(=O)N1CCCC1
Solvent: ClCCCl
Solvent: CCN(CC)CC
Solvent: O
Product: C[C@H](OC(=O)C(Br)c1ccc(Cl)cc1)C(=O)N1CCCC1
Temperature: 25 °C
Reaction time: 2 h
Yield: 58.9 %

Procedure:
To a solution of (2S)-2-hydroxy-1-(pyrrolidin-1-yl)propan-1-one (24.0 g, 0.17 mol) in DCE (120 mL) was added triethylamine (84.69 g, 0.84 mol) and 2-bromo-2-(4-chlorophenyl)acetyl chloride (crude, 46.29 g, 0.17 mol) at 0° C. The reaction mixture was stirred for 2 h at RT. The reaction mixture was diluted with water (200 mL) and separated the organic layer. The organic layer was washed with 10% NaS2O3 (100 mL) and saturated sodium bicarbonate (60 mL). The organic layer was dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified by flash column on 100-200 mesh silica-gel (20-25% ethyl acetate-hexane) to afford (2S)-1-oxo-1-(pyrrolidin-1-yl)propan-2-yl 2-bromo-2-(4-chlorophenyl)acetate 4 (37.5 g, 59%) as brown sticky gum.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[CH:9]([S:13]([C:16]1[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][CH:17]=1)(=[O:15])=[O:14])[NH:10][CH:11]=O.P(Cl)(Cl)(Cl)=O.N1C(C)=CC=CC=1C>C1COCC1>[C:19]1([CH3:22])[CH:18]=[CH:17][C:16]([S:13]([CH:9]([N+:10]#[C-:11])[C:3]2[C:2]([F:1])=[CH:7][CH:6]=[CH:5][C:4]=2[F:8])(=[O:15])=[O:14])=[CH:21][CH:20]=1
Reactant: Cc1ccc(S(=O)(=O)C(NC=O)c2c(F)cccc2F)cc1
Solvent: O=P(Cl)(Cl)Cl
Solvent: Cc1cccc(C)n1
Solvent: C1CCOC1
Product: [C-]#[N+]C(c1c(F)cccc1F)S(=O)(=O)c1ccc(C)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a mixture of N-[(2,6-Difluoro-phenyl)-(toluene-4-sulfonyl)-methyl]-formamide (2.07 g, 6.36 mmol) and THF (15 mL) is added phosphorous oxychloride (POCl3) (1.19 mL, 12.7 mmol) over a period of 5 minutes, and the resulting mixture stirred at room temperature for 10 minutes. The reaction is then cooled to 4° C. using an ice/water bath and 2,6-lutidine (4.45 mL, 38.2 mmol) is added over 30 minutes, maintaining the temperature less than 12° C. The cooling bath is removed and the mixture stirred at room temperature for 18 hours. The reaction mixture is poured into a stirred, ice water cooled solution of ice and saturated aqueous sodium bicarbonate (NaHCO3). The mixture is extracted with ethyl acetate (2×). The combined organic extracts are washed with 1N aqueous hydrochloric acid (30.0 mL), saturated aqueous sodium bicarbonate (NaHCO3) (30.0 mL), brine (30.0 mL) and dried (MgSO4). The solvents are removed in vacuo, and isopropanol (18.0 mL) is added to the residual brownish solid. The resulting slurry is stirred at room temperature for 2 hours, then water is added and the slurry stirred for an additional 30 minutes at room temperature. The slurry is filtered, the cake washed with 2:1 isopropanol-water (2×) and dried in a vacuum-oven (30° C.) for 48 hours. The title compound may be obtained as a tan solid (1.33 g, 68%).
Reaction SMILES: C([O:3][C:4]([C:6](=O)[CH:7]([CH3:20])[CH:8]([C:10]1[CH:15]=[CH:14][C:13]([C:16]([F:19])([F:18])[F:17])=[CH:12][CH:11]=1)[O-])=[O:5])C.[Li+].Cl.[Cl:24][C:25]1[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=1[NH:32][NH2:33].S(=O)(=O)(O)O>C(O)C>[Cl:24][C:25]1[CH:30]=[C:29]([Cl:31])[CH:28]=[CH:27][C:26]=1[N:32]1[C:8]([C:10]2[CH:11]=[CH:12][C:13]([C:16]([F:17])([F:18])[F:19])=[CH:14][CH:15]=2)=[C:7]([CH3:20])[C:6]([C:4]([OH:3])=[O:5])=[N:33]1
Reactant: NNc1ccc(Cl)cc1Cl
Reactant: CCOC(=O)C(=O)C(C)C([O-])c1ccc(C(F)(F)F)cc1
Agent: Cl
Agent: O=S(=O)(O)O
Agent: [Li+]
Solvent: CCO
Product: Cc1c(C(=O)O)nn(-c2ccc(Cl)cc2Cl)c1-c1ccc(C(F)(F)F)cc1
Temperature: 25 °C

Procedure:
A solution of 10 g of Lithium 3-ethoxycarbonyl-2-methyl-3-oxo-1-(4-trifluoromethyl-phenyl)-propan-1-olate, 6.9 g of (2,4-Dichloro-phenyl)-hydrazine hydrochloride and 74 ml of sulfuric acid (50%) in 184 ml of ethanol was heated to reflux for 7 h. After cooling to room temperature the organic solvents were removed under reduced pressure and the residue was diluted with 100 ml of water and extracted with ethyl acetate. The combined organic layers were dried over MgSO4 and the solvent was removed under reduced pressure. The residue was dissolved in 100 ml THF and a solution of 1.4 g of LiOH in 20 ml water was added at room temperature. The reaction mixture was heated to 60° C. for 7 h. Then, after cooling to room temperature the mixture was acidified to pH 1 by addition of half-concentrated hydrochloric acid. The precipitating product was collected by filtration and washed with water. The residue was codistilled twice with dichloromethane and twice with toluene. The isolated crude product was used in the next reaction step. Yield: 13 g.
Reaction SMILES: [CH3:1][C:2]([NH:4][C:5]1[C:10]([I:11])=[C:9]([NH:12][C:13]([CH3:15])=[O:14])[C:8]([I:16])=[C:7]([C:17]([O-:19])=[O:18])[C:6]=1[I:20])=[O:3].[Na+].Br[CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28].O>CN(C=O)C>[C:13]([NH:12][C:9]1[C:8]([I:16])=[C:7]([C:6]([I:20])=[C:5]([NH:4][C:2](=[O:3])[CH3:1])[C:10]=1[I:11])[C:17]([O:19][CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])=[O:18])(=[O:14])[CH3:15]
Reactant: CCOC(=O)CCCCBr
Reactant: CC(=O)Nc1c(I)c(NC(C)=O)c(I)c(C(=O)[O-])c1I
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CCCCOC(=O)c1c(I)c(NC(C)=O)c(I)c(NC(C)=O)c1I
Temperature: 25 °C
Reaction time: 12 h
Yield: 97.3 %

Procedure:
To a stirred solution of sodium diatrizoate (59.0 g, 92.8 mmol) in 350 ml of dry DMF was added ethyl 5-bromovalerate (14.7 ml, 92.8 mmol) in two portions and the resulting solution was stirred at ambient temperature for 12 hr. The reaction mixture was poured into 3.5 1 of water and the resulting white precipitate was collected, washed with ether and then air dried. The crude product was dissolved in acetonitrile-ethanol (5:2), filtered through a pad of silica gel and the filtrate was evaporated to give a solid (67 g, 97%). Recrystallization from methanol-water gave analytically pure product (mp 237°-239° C.) after drying under high vacuum; CI-MS: MH+ 743. The 1H-NMR (300 MHz) spectral data was consistent with the desired product. Calculated for C18H21I3N2O6 ; C 29.13, H 2.85, I 51.30; Found: C 29.13, H 2.78, I 51.15, N 3.75.
Reaction SMILES: [CH:1]12[O:12][CH:4]([CH:5]3[C:10](=[O:11])[O:9][C:7](=[O:8])[CH:6]31)[CH:3]=[CH:2]2.[C:13]([O:17][CH2:18][CH2:19][OH:20])(=[O:16])[CH:14]=[CH2:15]>C1(C)C=CC=CC=1>[C:10]([CH:5]1[CH:6]([C:7]([O:20][CH2:19][CH2:18][O:17][C:13](=[O:16])[CH:14]=[CH2:15])=[O:8])[CH:1]2[O:12][CH:4]1[CH:3]=[CH:2]2)([OH:9])=[O:11]
Reactant: O=C1OC(=O)C2C3C=CC(O3)C12
Reactant: C=CC(=O)OCCO
Solvent: Cc1ccccc1
Product: C=CC(=O)OCCOC(=O)C1C2C=CC(O2)C1C(=O)O

Procedure:
Maleic anhydride (50 g) and furan (150 ml) were heated under reflux for 1 hour, and then the excess of furan was distilled off. The residue was recrystallised from chloroform, yielding 72 g of 7-oxabicyclo [2.2.1]hept-2-ene-5,6-dicarboxylic acid anhydride (m.pt. 110° C., decomp.). This anhydride (40 g) and 30.75 g of 2-hydroxyethyl acrylate were heated in 250 ml of toluene at 100° C. for 3 hours, and then the toluene was distilled off under reduced pressure, leaving the desired compound as a viscous liquid.
Reaction SMILES: [C:1]1([CH3:14])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[S:9]([O:12][NH2:13])(=[O:11])=[O:10].[S:15]1[CH:19]=[CH:18][N:17]=[C:16]1[CH:20]([OH:22])[CH3:21]>ClCCl.CCOCC>[C:1]1([CH3:14])[CH:6]=[C:5]([CH3:7])[CH:4]=[C:3]([CH3:8])[C:2]=1[S:9]([O-:12])(=[O:11])=[O:10].[NH2:13][N+:17]1[CH:18]=[CH:19][S:15][C:16]=1[CH:20]([OH:22])[CH3:21]
Reactant: Cc1cc(C)c(S(=O)(=O)ON)c(C)c1
Reactant: CC(O)c1nccs1
Solvent: ClCCl
Solvent: CCOCC
Product: CC(O)c1scc[n+]1N
Product: Cc1cc(C)c(S(=O)(=O)[O-])c(C)c1
Reaction time: 12 h
Yield: 80.1 %

Procedure:
O-(Mesitylenesulfonyl)hydroxylamine containing ca. 18% water (1.95 g, 1.60 g dry wt., ca. 7.4 mmole) was dissolved in dichloromethane (12 mL) and dried over Na2SO4 and filtered. This was added dropwise to a solution of 1-(2-thiazolyl)ethanol (0.8 g, 6.2 mmole) in dichloromethane (4 mL) at 0 C. After stirring an additional 12 hr at 4 C, the mixture was diluted with ether (13 mL) and stored at 4 C for 1 hr. The supernatant was decanted from the syrupy precipitate, which was triturated with 1:1 dichloromethane-ether (10 mL) to yield a powder which was filtered out, washed with the same solvent, and dried to yield 1.71 g of the title compound, mp 105–107 C.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([OH:11])[CH:9]=2)[CH:4]=[CH:3][CH:2]=1.CN(C)C=O.N1C=CN=C1.[Si:22](Cl)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]>>[Si:22]([O:11][C:8]1[CH:9]=[C:10]2[C:5]([CH:4]=[CH:3][CH:2]=[N:1]2)=[CH:6][CH:7]=1)([C:25]([CH3:28])([CH3:27])[CH3:26])([CH3:24])[CH3:23]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: Oc1ccc2cccnc2c1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)[Si](C)(C)Oc1ccc2cccnc2c1

Procedure:
At room temperature to a solution of quinolin-7-ol (Matrix Scientific, Cat. No. 007603; 0.6 g, 4 mmol) in N,N-Dimethylformamide (10 mL, 100 mmol) was added 1H-imidazole (0.670 g, 9.84 mmol), followed by tert-butyldimethylsilyl chloride (0.934 g, 6.20 mmol) with stirring. The mixture was stirred at room temperature overnight, then quenched with sat'd NaHCO3 solution, and extracted with methylene chloride (3×). The combined extracts were washed with water and brine successively, and then dried over Na2SO4. After filtration, the filtrate was concentrated and purified with flash column using 15% ethyl acetate in hexane as eluent to yield 0.88 g of the product. LCMS (M+H)+: m/z=260.3.
Reaction SMILES: [N:1]([O-])=O.[Na+].[Cl:5][C:6]1[CH:22]=[CH:21][C:9]([O:10][C:11]2[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][C:12]=2[N+:18]([O-:20])=[O:19])=[CH:8][CH:7]=1.C(O)C.O.O.[Sn](Cl)Cl>O.Cl>[Cl:5][C:6]1[CH:22]=[CH:21][C:9]([O:10][C:11]2[CH:17]=[CH:16][C:14]([NH:15][NH2:1])=[CH:13][C:12]=2[N+:18]([O-:20])=[O:19])=[CH:8][CH:7]=1
Reactant: Nc1ccc(Oc2ccc(Cl)cc2)c([N+](=O)[O-])c1
Reactant: O=N[O-]
Agent: Cl
Agent: Cl[Sn]Cl
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: NNc1ccc(Oc2ccc(Cl)cc2)c([N+](=O)[O-])c1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
A solution of 0.52 g of sodium nitrite in 5 ml of water was added dropwise to a stirred mixture consisting of 1.9 g of 4-(4-chlorophenoxy)-3-nitroaniline, 25 ml of concentrated hydrochloric acid and 25 ml of ethanol cooled to 0° C., and the mixture was then stirred at 0° C. for 60 min and subsequently added dropwise to a suspension of 8.5 g of tin dichloride dihydrate in 8 ml of concentrated HCl. The precipitate was filtered off with suction, washed with water, suspended in 200 ml of water under nitrogen and decomposed with 100 ml of 30% strength sodium hydroxide solution at 10-15° C. The oil formed was extracted by shaking with ethyl acetate and washed with water, and the organic phase was dried with sodium sulfate. The product was then precipitated with isopropanolic HCl, filtered off with suction and dried in vacuo.
Reaction SMILES: [CH:1]1([NH:4][C:5]2[N:10]3[N:11]=[CH:12][C:13]([CH:14]=O)=[C:9]3[N:8]=[C:7]([NH:16][C:17](=[O:20])[O:18][CH3:19])[CH:6]=2)[CH2:3][CH2:2]1.[NH:21]1[CH2:27][C:25](=[O:26])[NH:24][C:22]1=[O:23].N1CCCCC1>C(O)C>[CH:1]1([NH:4][C:5]2[N:10]3[N:11]=[CH:12][C:13](/[CH:14]=[C:27]4\[NH:21][C:22](=[O:23])[NH:24][C:25]\4=[O:26])=[C:9]3[N:8]=[C:7]([NH:16][C:17](=[O:20])[O:18][CH3:19])[CH:6]=2)[CH2:3][CH2:2]1
Reactant: COC(=O)Nc1cc(NC2CC2)n2ncc(C=O)c2n1
Reactant: O=C1CNC(=O)N1
Solvent: CCO
Solvent: C1CCNCC1
Product: COC(=O)Nc1cc(NC2CC2)n2ncc(/C=C3\NC(=O)NC3=O)c2n1
Temperature: 80 °C
Yield: 35 %

Procedure:
To methyl 7-(cyclopropylamino)-3-formylpyrazolo[1,5-a]pyrimidin-5-ylcarbamate (33 mg, 0.12 mmol) in 1.0 mL ethanol was added hydantoin (12 mg, 0.12 mmol) and piperidine (11 ul). The reaction was heated at 80° C. for two hours. The reaction was cooled to room temperature, the yellow precipitate was filtered, and washed with ethanol to yield 15 mg (40% yield) (Z)-methyl 7-(cyclopropylamino)-3-((2,5-dioxoimidazolidin-4-ylidene) methyl)pyrazolo [1,5-a]pyrimidin-5-ylcarbamate. LCMS (M+1=358)