Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][N:2]([CH3:13])[S:3]([C:6]1[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=1)(=[O:5])=[O:4].[OH-].[Na+].Cl[C:17]1[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:18]=1[C:19]#[N:20].O>CS(C)=O>[CH3:1][N:2]([CH3:13])[S:3]([C:6]1[CH:11]=[CH:10][C:9]([O:12][C:17]2[CH:24]=[CH:23][C:22]([N+:25]([O-:27])=[O:26])=[CH:21][C:18]=2[C:19]#[N:20])=[CH:8][CH:7]=1)(=[O:4])=[O:5]
Reactant: CN(C)S(=O)(=O)c1ccc(O)cc1
Reactant: N#Cc1cc([N+](=O)[O-])ccc1Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CS(C)=O
Product: CN(C)S(=O)(=O)c1ccc(Oc2ccc([N+](=O)[O-])cc2C#N)cc1
Temperature: 60 °C
Yield: 79.9 %

Procedure:
To a solution of 6.37 g (0.0317 moles) of N,N-dimethyl-4-hydroxybenzenesulfonamide in 150 ml of DMSO was added 1.27 g (0.0317 moles) of NaOH. The mixture was heated to 60° C. and 5.26 g (0.288 moles) of 2-chloro-5-nitrobenzonitrile added and the mixture heated at 75° C. for 21/2 hrs. The reaction mixture was cooled and poured into a solution of 400 ml of 2 N aqueous NaOH and 300 ml of water. The product was collected by filtration, washed well with water and dried to obtain 8.8 g of product (88% yield). Recrystallization from a mixture of ethanol and dimethylformamide afforded purified N,N-dimethyl-4-(2-cyano-4-nitrophenoxy)benzenesulfonamide, mp 221.5°-223° C.
Reaction SMILES: [Cl:1][C:2]1[C:14]([Cl:15])=[C:13]([O:16][CH2:17][C:18]([O:20]CC)=[O:19])[CH:12]=[C:11]2[C:3]=1[C:4]1[C:9]([CH:23]3[CH2:25][CH2:24]3)([CH2:10]2)[CH2:8][CH2:7][C:6](=[O:26])[CH:5]=1.[OH-].[Na+]>CO>[Cl:1][C:2]1[C:14]([Cl:15])=[C:13]([O:16][CH2:17][C:18]([OH:20])=[O:19])[CH:12]=[C:11]2[C:3]=1[C:4]1[C:9]([CH:23]3[CH2:24][CH2:25]3)([CH2:10]2)[CH2:8][CH2:7][C:6](=[O:26])[CH:5]=1
Reactant: CCOC(=O)COc1cc2c(c(Cl)c1Cl)C1=CC(=O)CCC1(C1CC1)C2
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(O)COc1cc2c(c(Cl)c1Cl)C1=CC(=O)CCC1(C1CC1)C2

Procedure:
Ethyl [(5,6-dichloro-9a-cyclopropyl-3-oxo-1,2,9,9a-tetrahydro-3H-fluoren-7yl)oxy]acetate (4.2 gm., 0.011 mole) is added to a solution composed of 20% aqueous sodium hydroxide solution (4.32 ml., 0.022 mole) and methanol (45 ml.). The mixture is stirred and heated at reflux for two hours and then concentrated in vacuo at 50° C. The residue is dissolved in water (50 ml.) and made acid to Congo red paper with 6 normal hydrochloric acid. The solid that separates is removed by filtration, washed with water, then with a little methanol and finally with a little ether. After drying, the product is recrystallized from acetic acid to give pure [(5,6-dichloro-3-oxo-9a-cyclopropyl-1,2,9,9a-tetrahydro-3H-fluoren-7-yl)oxy]acetic acid.
Reaction SMILES: Cl.Cl.[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH2:11])[CH2:4]2.[NH:12]1[CH:16]=[C:15](/[CH:17]=[CH:18]/[C:19](O)=[O:20])[N:14]=[CH:13]1>>[N:3]12[CH2:10][CH2:9][CH:6]([CH2:7][CH2:8]1)[C@@H:5]([NH:11][C:19](=[O:20])/[CH:18]=[CH:17]/[C:15]1[N:14]=[CH:13][NH:12][CH:16]=1)[CH2:4]2
Reactant: N[C@H]1CN2CCC1CC2
Reactant: O=C(O)/C=C/c1c[nH]cn1
Agent: Cl
Product: O=C(/C=C/c1c[nH]cn1)N[C@H]1CN2CCC1CC2

Procedure:
Prepared as a free base by a method analogous to that described in Example 1 from (R)-1-azabicyclo[2.2.2]oct-3-ylamine dihydrochloride and E-3-(4-imidazolyl)propenoic acid; the compound was purified by chromatography on silica gel using ammoniated methanol/chloroform mixtures as the eluent; MS (ES+) 247 (MH+).
Reaction SMILES: [CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=2)[CH:6]=1.C(Cl)(=O)C([Cl:19])=O>ClCCl.CN(C)C=O>[CH3:1][C:2]1[N:3]=[CH:4][N:5]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([Cl:19])=[O:12])=[CH:9][CH:8]=2)[CH:6]=1
Reactant: Cc1cn(-c2ccc(C(=O)O)cc2)cn1
Reactant: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cc1cn(-c2ccc(C(=O)Cl)cc2)cn1
Temperature: 25 °C
Reaction time: 18 h
Yield: 117.3 %

Procedure:
To a suspension of 4-(4-methylimidazol-1-yl)benzoic acid (0.80 g) in dichloromethane (25 ml) was added oxalyl chloride (0.50 g) and one drop of dimethylformamide. The mixture was stirred at room temperature for 18 hours and the volatile material was removed under reduced pressure to yield 4-(4-methylimidazol-1-yl)benzoyl chloride (1.02 g), which was utilized without further purification.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([C:8]2[N:13]=[C:12]([C:14]3[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=3)[CH:11]=[C:10]([C:21]([F:24])([F:23])[F:22])[N:9]=2)[CH:5]=[CH:6][CH:7]=1.[C:25]([NH:29][S:30]([C:33]1[CH:34]=[C:35](B(O)O)[CH:36]=[CH:37][CH:38]=1)(=[O:32])=[O:31])([CH3:28])([CH3:27])[CH3:26]>>[C:25]([NH:29][S:30]([C:33]1[CH:38]=[C:37]([C:2]2[CH:7]=[CH:6][CH:5]=[C:4]([C:8]3[N:13]=[C:12]([C:14]4[CH:19]=[CH:18][C:17]([F:20])=[CH:16][CH:15]=4)[CH:11]=[C:10]([C:21]([F:23])([F:24])[F:22])[N:9]=3)[CH:3]=2)[CH:36]=[CH:35][CH:34]=1)(=[O:32])=[O:31])([CH3:28])([CH3:26])[CH3:27]
Reactant: Fc1ccc(-c2cc(C(F)(F)F)nc(-c3cccc(Br)c3)n2)cc1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(B(O)O)c1
Product: CC(C)(C)NS(=O)(=O)c1cccc(-c2cccc(-c3nc(-c4ccc(F)cc4)cc(C(F)(F)F)n3)c2)c1

Procedure:
3′-[4-(4-fluoro-phenyl)-6-trifluoromethyl-pyrimidin-2-yl]-biphenyl-3-sulfonic acid tert-butylamide was prepared from 2-(3-bromo-phenyl)-4-(4-fluoro-phenyl)-6-trifluoromethyl-pyrimidine (example E.102) (0.40 g, 1.0 mmol) and commercially available 3-(tert.-butylsulfamoyl)-phenylboronic acid (0.31 g, 1.2 mmol) according to the general procedure VI. Obtained as white foam (0.49 g), which was subsequently deprotected.
Reaction SMILES: [Cl:1][C:2]1[CH:49]=[CH:48][C:5]([C:6]2[C:11]([C:12]3[CH:21]=[CH:20][C:19]4[C:14](=[CH:15][CH:16]=[C:17]([C:22]5[N:26]([CH:27]6[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]6)[C:25]6[CH:33]=[CH:34][C:35]([C:37]([OH:39])=[O:38])=[CH:36][C:24]=6[N:23]=5)[CH:18]=4)[N:13]=3)=[CH:10][C:9]([C:40](=[O:47])[NH:41][CH2:42][CH2:43][N:44](C)C)=[CH:8][CH:7]=2)=[CH:4][CH:3]=1.NCC(N)=[O:53]>>[C:43]([CH2:42][NH:41][C:40]([C:9]1[CH:10]=[C:11]([C:12]2[CH:21]=[CH:20][C:19]3[C:14](=[CH:15][CH:16]=[C:17]([C:22]4[N:26]([CH:27]5[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]5)[C:25]5[CH:33]=[CH:34][C:35]([C:37]([OH:39])=[O:38])=[CH:36][C:24]=5[N:23]=4)[CH:18]=3)[N:13]=2)[C:6]([C:5]2[CH:48]=[CH:49][C:2]([Cl:1])=[CH:3][CH:4]=2)=[CH:7][CH:8]=1)=[O:47])(=[O:53])[NH2:44]
Reactant: CN(C)CCNC(=O)c1ccc(-c2ccc(Cl)cc2)c(-c2ccc3cc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)ccc3n2)c1
Reactant: NCC(N)=O
Product: NC(=O)CNC(=O)c1ccc(-c2ccc(Cl)cc2)c(-c2ccc3cc(-c4nc5cc(C(=O)O)ccc5n4C4CCCCC4)ccc3n2)c1

Procedure:
The title compound was synthesized as described for Compound 491, except glycine-amide was used instead of N1,N1-dimethyl-ethane-1,2-diamine.
Reaction SMILES: [CH2:1]1[CH2:8][NH:7][S:4](=[O:6])(=[O:5])[CH2:3][CH2:2]1.Br[C:10]1[N:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[O:21])[C:17]([OH:31])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2>N1C=CC=CC=1>[O:5]=[S:4]1(=[O:6])[CH2:3][CH2:2][CH2:1][CH2:8][N:7]1[C:10]1[N:19]=[C:18]([C:20]([NH:22][CH2:23][C:24]2[CH:29]=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)=[O:21])[C:17]([OH:31])=[C:16]2[C:11]=1[CH:12]=[CH:13][CH:14]=[N:15]2
Reactant: O=C(NCc1ccc(F)cc1)c1nc(Br)c2cccnc2c1O
Reactant: O=S1(=O)CCCCN1
Solvent: c1ccncc1
Product: O=C(NCc1ccc(F)cc1)c1nc(N2CCCCS2(=O)=O)c2cccnc2c1O
Temperature: 25 °C
Reaction time: 16 h

Procedure:
To a mixture of 1,4 butanesultam (prepared as in White et al, J. Org Chem. 1987, 52: 2162) (1.00 g, 7.40 mmol), 5-bromo-N-(4-fluorobenzyl)-8-hydroxy-1,6-naphthyridine-7-carboxamide (3.06 g, 8.14 mmol), and Cu2O (1.06 g, 7.40 mmol) under an atmosphere of argon was added pyridine (50 mL), and the suspension was stirred at reflux for 16 hr. The reaction was allowed to cool to room temperature and filtered to remove the solids. The solids were washed with chloroform (500 mL). The resulting filtrate was evaporated to dryness and the residue was dissolved in chloroform (1L) and vigorously stirred with a slurry of EDTA (4.0 g) in water (150 mL). After a period of 16 hr, the chloroform extracts were dried (Na2SO4) and evaporated in vacuo. The residue was purified by reverse phase HPLC. (Waters PrePak 500 cartridge C18, Gradient elution with Water:Acetonitrile 95:5 to 5:95 with 0.1% TFA at 75 mL/min over 45 mins). Lyophilization of the pure fractions afforded the title compound as an off-white solid.
Reaction SMILES: [C:1]1([CH3:54])[CH:6]=[CH:5][C:4]([S:7]([S:10][C@H:11]2[N:14]([C:15](=[C:32](OS(C(F)(F)F)(=O)=O)[CH3:33])[C:16]([O:18][CH:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[C:13](=[O:42])[C@H:12]2[NH:43][C:44](=[O:53])[CH2:45][O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)(=[O:9])=[O:8])=[CH:3][CH:2]=1.C(N(CC)CC)C>O1CCCC1>[C:1]1([CH3:54])[CH:6]=[CH:5][C:4]([S:7]([S:10][C@H:11]2[N:14]([C:15](=[C:32]=[CH2:33])[C:16]([O:18][CH:19]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[O:17])[C:13](=[O:42])[C@H:12]2[NH:43][C:44](=[O:53])[CH2:45][O:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)(=[O:8])=[O:9])=[CH:3][CH:2]=1
Reactant: CC(OS(=O)(=O)C(F)(F)F)=C(C(=O)OC(c1ccccc1)c1ccccc1)N1C(=O)[C@@H](NC(=O)COc2ccccc2)[C@H]1SS(=O)(=O)c1ccc(C)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: C=C=C(C(=O)OC(c1ccccc1)c1ccccc1)N1C(=O)[C@@H](NC(=O)COc2ccccc2)[C@H]1SS(=O)(=O)c1ccc(C)cc1
Yield: 103.9 %

Procedure:
Embodiment a: A solution of diphenylmethyl 2-[(3R,4R)-4-(p-toluenesulfonylthio)-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-3-trifluoromethanesulfonyloxy-2-butenoate (XVa, 0.300 g, 0.00036 mole) in dry tetrahydrofuran (3 mL) was treated with triethylamine (0.077 mL, 0.00036 mole) for 1 h at room temperature. Reverse-phase chromatography (C-18 column, eluting with 65% acetonitrile - 35% of 0.01M phosphate pH 6.5 buffer) showed complete consumption of the starting material after 45 min with formation of a single, faster-eluting product. 0.05M sulfuric acid and ethyl acetate was added to the reaction mixture, followed by separating the two phases. The organic phase was dried with sodium sulfate and evaporated to give 0.245g of diphenylmethyl 2-[(3R,4R)-4-(p-toluenesulfonylthio)-3-phenoxyacetamido-2-oxo-azetidin-1-yl]-2,3-butadienoate (Ia) as a colorless foam (quantitative yield).