Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]([NH2:18])=[S:17])=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Br[CH2:20][C:21](=O)[CH2:22][CH3:23].C(N(CC)CC)C>C(O)C>[CH2:1]([O:8][C:9]1[C:10]([NH:15][C:16]2[S:17][CH:20]=[C:21]([CH2:22][CH3:23])[N:18]=2)=[N:11][CH:12]=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: NC(=S)Nc1ncccc1OCc1ccccc1
Reactant: CCC(=O)CBr
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCc1csc(Nc2ncccc2OCc2ccccc2)n1
Yield: 96.8 %

Procedure:
Following the procedure of Example 2, Step C, 1-(3-(benzyloxy)pyridin-2-yl)thiourea (525 mg, 2.02 mmol), 1-bromobutan-2-one (428 mg, 2.83 mmol), and triethylamine (0.480 mL, 3.44 mmol) were reacted in ethanol (20 mL) to provide N-(3-(benzyloxy)pyridin-2-yl)-4-ethylthiazol-2-amine (609 mg) as a yellow oil. The HCl salt was prepared according to Example 3, Step C, to provide N-(3-(benzyloxy)pyridin-2-yl)-4-ethylthiazol-2-amine hydrochloride (585 mg, 83%) as a white powder. 1H NMR (d6-DMSO) δ 7.97 (d, 1H), 7.59-7.61 (m, 3H), 7.35-7.42 (m, 3H), 7.12 (m, 1H), 6.86 (s, 1H), 5.34 (s, 2H), 2.67 (q, 2H), 1.23 (t, 3H). Mass spectrum (apci) m/z=312 (100) (M+H-HCl).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([OH:11])[CH:6]=[CH:7][C:8]=1[O:9][CH3:10].C1N2CN3CN(C2)CN1C3.Cl.FC(F)(F)[C:25](O)=[O:26]>>[OH:11][C:5]1[CH:4]=[C:3]([O:2][CH3:1])[C:8]([O:9][CH3:10])=[CH:7][C:6]=1[CH:25]=[O:26]
Reactant: O=C(O)C(F)(F)F
Reactant: COc1ccc(O)cc1OC
Agent: C1N2CN3CN1CN(C2)C3
Agent: Cl
Product: COc1cc(O)c(C=O)cc1OC
Reaction time: 0.25 h

Procedure:
In a 500 mL recovery flask, 5.0 g (32.4 mmol) of 3,4-dimethoxyphenol (manufactured by Tokyo Chemical Industry Co., Ltd.) and 18.2 g (130 mmol, 4.0 eq) of hexamethylenetetramine (manufactured by Tokyo Chemical Industry Co., Ltd.) were dissolved in 100 ml of trifluoroacetic acid (manufactured by Kanto Chemical Co., Inc.) and reacted at 100° C. for 24 hours. After the reaction was completed, in an ice bath, 200 ml of 1 N hydrochloric acid was added thereto and the resultant was stirred for 15 minutes. After the stirring was completed, the resultant was extracted with chloroform to obtain an extract. The extract was washed with hydrochloric acid and saturated saline, thereby obtaining 2.17 g (11.0 mmol) of 2-hydroxy-4,5-dimethoxybenzaldehyde.
Reaction SMILES: FC1C(F)=CC=CC=1C1C=C[C:12]([O:15]CCCCCCOC(=O)C=C)=[CH:11][CH:10]=1.[Br:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][OH:36].BrCCCCCCO>>[C:12]([O:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][Br:27])(=[O:15])[CH:11]=[CH2:10]
Reactant: OCCCCCCCCBr
Reactant: C=CC(=O)OCCCCCCOc1ccc(-c2cccc(F)c2F)cc1
Agent: OCCCCCCBr
Product: C=CC(=O)OCCCCCCCCBr
Yield: 78 %

Procedure:
The same procedure as in the synthesis (a) of Example 2 was repeated except that 34.7 g of 8-bromo-1-octanol were used instead of 30 g of 6-bromo-1-hexanol to give 34.1 g (Y., 78%) of 8-acryloyloxy-1-bromooctane. GC; 97%
Reaction SMILES: Br[CH:2]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][CH:9]=1)[C:3]([O:5][CH2:6][CH3:7])=[O:4].[SH:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1>>[CH2:6]([O:5][C:3](=[O:4])[CH:2]([S:19][C:20]1[CH:25]=[CH:24][C:23]([OH:26])=[CH:22][CH:21]=1)[C:8]1[CH:13]=[CH:12][C:11]([C:14]2[S:15][CH:16]=[CH:17][CH:18]=2)=[CH:10][CH:9]=1)[CH3:7]
Reactant: CCOC(=O)C(Br)c1ccc(-c2cccs2)cc1
Reactant: Oc1ccc(S)cc1
Product: CCOC(=O)C(Sc1ccc(O)cc1)c1ccc(-c2cccs2)cc1
Yield: 73 %

Procedure:
Ethyl[(4-hydroxyphenyl)sulfanyl][4-(2-thienyl)phenyl]acetate was prepared according to the general method as outlined in example 1 (step 1), starting from ethyl bromo[4-(2-thienyl)phenyl]acetate (2 g, 6.15 mmol) and 4-mercaptophenol (0.82 g, 6.5 mmol); 1.68 g white solid. mp: 103° C.; Yield 73%; MS: 369.1 (M−H)−
Reaction SMILES: [H-].[Na+].[Br-].[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CS(C)=O.[CH3:34][C:35](=O)[CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43]>O>[CH3:34][CH:35]([CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH2:42][CH3:43])[CH2:10][CH2:9][CH2:8][CH2:7][CH:6]=[CH:5][OH:4]
Reactant: OCCCCCC[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: CCCCCCCCC(C)=O
Agent: [Br-]
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: CCCCCCCCC(C)CCCCC=CO
Temperature: 70 °C
Reaction time: 18 h
Yield: 49.5 %

Procedure:
Into a dried 5L, 3 neck round bottom flask fitted with mechanical stirring, nitrogen inlet, dropping funnel, thermometer and nitrogen outlet is added 80 g of 60% sodium hydride (2.0 mol) in mineral oil. The mineral oil is removed by washing with hexanes. Anhydrous dimethyl sulfoxide (500 ml) is added to the flask and heated to 70° C. until evolution of hydrogen stops. The reaction mixture is cooled to room temperature followed by addition of 1L of anhydrous tetrahydrofuran. (6-hydroxyhexyl) triphenylphosphonium bromide (443.4 g, 1 mol) is slurried with warm anhydrous dimethyl sulfoxide (50° C., 500 ml) and slowly added to the reaction mixture thru the dropping funnel while keeping the reaction at 25-30° C. The reaction is stirred for 30 minutes at room temperature at which time 2-decanone (171.9 g, 1.1 mol) is slowly added thru a dropping funnel. Reaction is slightly exothermic and cooling is needed to maintain 25-30° C. Mixture is stirred for 18 hrs. and then poured into a separatory funnel containing 600 ml of purified water and 300 ml of hexanes. After shaking the oil phase (top) is allowed to separate out and the water phase is removed. The extractions of the oil phase are continued using water until both phases are clear. The organic phase is collected, vacuum distilled and purified by liquid chromatography (90:10 hexanes:ethyl acetate, silica gel stationary phase) to obtain a clear, oily product (119.1 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][C:9]2[C:18]([CH:19]=[C:20]3[S:24][C:23](=[O:25])[NH:22][C:21]3=[O:26])=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[CH:4][CH:3]=1.ClC1C=C(C=CC=1)C(OO)=[O:32]>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([S:8]([C:9]2[C:18]([CH:19]=[C:20]3[S:24][C:23](=[O:25])[NH:22][C:21]3=[O:26])=[CH:17][C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[N:10]=2)=[O:32])=[CH:6][CH:7]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O=C1NC(=O)C(=Cc2cc3ccccc3nc2Sc2ccc(Cl)cc2)S1
Solvent: CO
Solvent: ClCCl
Product: O=C1NC(=O)C(=Cc2cc3ccccc3nc2S(=O)c2ccc(Cl)cc2)S1
Temperature: 25 °C
Reaction time: 4 h
Yield: 30 %

Procedure:
The compound prepared in Example 224 was dissolved in CH2Cl2/CH3OH (5:1), and to this solution was added 3-chloroperoxybenzoic acid (2 eq. of 77% max. purity). The mixture was stirring at RT for 4 hrs before TLC analysis showed the disappearance of the starting compound. The reaction mixture was stirring for an additionally 2 hrs. At the end of the reaction, white crystalline product precipitated. The product was collected by filteration, washed several times with ether, and air dried for 48 hrs to provide the final product with a yield of 30%.
Reaction SMILES: [CH2:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH2:10][CH3:11])[C:4]=1[C:12](=[O:24])[C:13]([NH:15][N:16]=[CH:17][C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[O:14])[CH3:2].S(OC)(O[CH3:29])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.O>[CH2:1]([C:3]1[CH:8]=[C:7]([CH3:9])[CH:6]=[C:5]([CH2:10][CH3:11])[C:4]=1[C:12](=[O:24])[C:13]([N:15]([CH3:29])[N:16]=[CH:17][C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1)=[O:14])[CH3:2]
Reactant: CCc1cc(C)cc(CC)c1C(=O)C(=O)NN=Cc1ccccc1
Reactant: COS(=O)(=O)OC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Solvent: O
Product: CCc1cc(C)cc(CC)c1C(=O)C(=O)N(C)N=Cc1ccccc1
Temperature: 5 °C
Reaction time: 24 h
Yield: 78.8 %

Procedure:
To a 25 mL volume two-necked flask, 500 mg of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-2-(phenylmethylidene)hydrazine ((40-a)-(14)-6), 2.3 ml of toluene, 345 mg of dimethyl sulfate and 315 mg of potassium carbonate were added and the mixture was stirred at 5° C. for 24 hours. To the reaction mixture, 2 ml of water and 2.3 ml of toluene were added and the resultant was extracted. Further, the aqueous layer was extracted with 2.5 ml of toluene two times. The organic layers were combined, concentrated under reduced pressure and subjected to column chromatography (hexane:ethyl acetate=5:1) to give 411 mg of 1-[2-(2,6-diethyl-4-methylphenyl)-2-oxoacetyl]-1-methyl-2-(phenylmethylidene)hydrazine ((40-b)-(15)-5).
Reaction SMILES: [SH:1][C:2]1[S:3][C:4]([CH2:8][C:9]([OH:11])=[O:10])=[C:5]([CH3:7])[N:6]=1.[C:12]([O:16][C:17](=[O:22])[C:18](Br)([CH3:20])[CH3:19])([CH3:15])([CH3:14])[CH3:13]>CO.[OH-].[Na+]>[C:12]([O:16][C:17](=[O:22])[C:18]([S:1][C:2]1[S:3][C:4]([CH2:8][C:9]([OH:11])=[O:10])=[C:5]([CH3:7])[N:6]=1)([CH3:20])[CH3:19])([CH3:15])([CH3:14])[CH3:13]
Reactant: Cc1nc(S)sc1CC(=O)O
Reactant: CC(C)(C)OC(=O)C(C)(C)Br
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: Cc1nc(SC(C)(C)C(=O)OC(C)(C)C)sc1CC(=O)O
Temperature: 60 °C
Reaction time: 6 h
Yield: 95.2 %

Procedure:
Commercially available (2-mercapto-4-methyl-1,3-thiazol-5-yl)acetic acid (15 g) was dissolved in methanol (360 mL) and 1N aqueous sodium hydroxide solution (174 mL), 2-bromo-2-methylpropionic acid tert-butyl ester (19.4 g) was added, and the mixture was stirred at 60° C. for 6 hr. The reaction mixture was concentrated, the residue was dissolved in water, and the mixture was acidified with 10% aqueous citric acid solution. The precipitated solid was collected by filtration, and dried under reduced pressure to give the title compound (25 g) as a white solid.
Reaction SMILES: [CH3:1][O:2][P:3]([CH2:7][C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])([O:5][CH3:6])=[O:4].[F:15][C:16]1[CH:25]=[CH:24][C:19]([O:20][CH2:21][CH2:22]Br)=[CH:18][CH:17]=1>>[F:15][C:16]1[CH:25]=[CH:24][C:19]([O:20][CH2:21][CH2:22][CH:7]([P:3]([O:5][CH3:6])([O:2][CH3:1])=[O:4])[C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])=[CH:18][CH:17]=1
Reactant: Fc1ccc(OCCBr)cc1
Reactant: COP(=O)(CC(=O)OC(C)(C)C)OC
Product: COP(=O)(OC)C(CCOc1ccc(F)cc1)C(=O)OC(C)(C)C
Yield: 61.6 %

Procedure:
20.5 g of tert-butyl dimethylphosphonoacetate were reacted with 25 g of 4-fluorophenoxyethyl bromide by the method described in Example 5 A). The reaction mixture was worked up as described in Example 5 A). 20.4 g of tert-butyl 4-(4-fluorophenoxy)-2-(dimethylphosphono)-n-butyrate were obtained.