Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [I-:1].[Na+].Br[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:16][CH:15]=2)=[CH:10][C:9]=1[C:25]1[CH:34]=[CH:33][C:32]2[C:31]([CH3:36])([CH3:35])[CH2:30][CH2:29][C:28]([CH3:38])([CH3:37])[C:27]=2[CH:26]=1>CC(C)=O>[I:1][CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]([O:22][CH2:23][CH3:24])=[O:21])=[CH:16][CH:15]=2)=[CH:10][C:9]=1[C:25]1[CH:34]=[CH:33][C:32]2[C:31]([CH3:36])([CH3:35])[CH2:30][CH2:29][C:28]([CH3:38])([CH3:37])[C:27]=2[CH:26]=1
Reactant: [I-]
Reactant: CCOC(=O)c1ccc(-c2ccc(OCCCBr)c(-c3ccc4c(c3)C(C)(C)CCC4(C)C)c2)cc1
Agent: [Na+]
Solvent: CC(C)=O
Product: CCOC(=O)c1ccc(-c2ccc(OCCCI)c(-c3ccc4c(c3)C(C)(C)CCC4(C)C)c2)cc1
Temperature: 25 °C
Reaction time: 8 h
Yield: 87.9 %

Procedure:
260 mg (1.73 mmol) of sodium iodide are added to a solution of 640 mg (1.16 mmol) of ethyl 4′-(3-bromopropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)biphenyl-4-carboxylate in 40 ml of acetone. The reaction mixture is stirred overnight at room temperature. The precipitate formed is filtered off and the filtrate is evaporated. 608 mg of ethyl 4′-(3-iodopropoxy)-3′-(5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphth-2-yl)biphenyl-4-carboxylate are obtained in the form of a white solid (m.p.=118° C., yield=71%).
Reaction SMILES: [N:1]1([CH:10]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH:11]([OH:14])[CH2:12][OH:13])[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[C:21]1([CH3:31])[CH:26]=[CH:25][C:24]([S:27](Cl)(=[O:29])=[O:28])=[CH:23][CH:22]=1>N1C=CC=CC=1.O>[OH:14][CH:11]([CH:10]([N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[CH2:12][O:13][S:27]([C:24]1[CH:25]=[CH:26][C:21]([CH3:31])=[CH:22][CH:23]=1)(=[O:29])=[O:28]
Reactant: OCC(O)C(c1ccccc1)n1ccc2ccccc21
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Solvent: O
Solvent: c1ccncc1
Product: Cc1ccc(S(=O)(=O)OCC(O)C(c2ccccc2)n2ccc3ccccc32)cc1
Yield: 69.1 %

Procedure:
A solution of (2RS,3RS)-3-indol-1-yl-3-phenyl-propane-1,2-diol (1.83 g, 6.8 mmol) and p-toluenesulfonyl chloride (1.31 g, 6.8 mmol) in anhydrous pyridine (10 mL) was stirred at room temperature under nitrogen for 15 hours. The mixture was then diluted with water (10 mL), quenched with a 2N aqueous solution of hydrochloric acid in an ice/water bath until the solution was pH=3, and extracted with dichloromethane. The organic layer was washed with water again, dried over anhydrous sodium sulfate, filtered, and concentrated. The residue was purified via Biotage chromatography (FlasH40i, silica, 10%, 25% EtOAc/hexane) to yield 1.98 g (69%) of (2RS,3RS)-toluene-4-sulfonic acid 2-hydroxy-3-indol-1-yl-3-phenyl-propyl ester as a white solid. 1HNMR (DMSO): δ3.70 and δ3.85 (dd and dd, 2H, CH2OTs), δ4.80 (m, 1H, CHOH), δ5.52 (d, 1H, CHPh), δ5.82 (d, 1H, CHOH); MS (ESI) m/z 422 ([M+H]+).
Reaction SMILES: [H-].[Na+].[Br:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[OH:11].[Na].[F:13][C:14]([F:22])([F:21])[CH2:15]CS([O-])(=O)=O>CN(C=O)C>[Br:3][C:4]1[CH:9]=[C:8]([Cl:10])[CH:7]=[CH:6][C:5]=1[O:11][CH2:15][C:14]([F:22])([F:21])[F:13]
Reactant: Oc1ccc(Cl)cc1Br
Reactant: O=S(=O)([O-])CCC(F)(F)F
Agent: [H-]
Agent: [Na+]
Agent: [Na]
Solvent: CN(C)C=O
Product: FC(F)(F)COc1ccc(Cl)cc1Br

Procedure:
To a stirred cold (0° C.) suspension of oil free NaH (0.12 mol, 4.8 g of 60% NaH in mineral oil) in anhydrous DMF (50 mL), a solution of 2-bromo-4-chlorophenol in DMF (50 mL) was added over 30 minutes under nitrogen. The resultant gray suspension of the sodium salt of 2-bromo-4-chlorophenol was treated with neat 2,2,2-trifluoroethylmethane sulfonate (21.4 g, 0.12 mol). The stirred mixture was heated at reflux temperature for 2-3 days. The mixture was cooled in an ice water bath and extracted with diethyl ether (2×100 mL). The combined ether extract was washed with 1N NaOH (3×100 mL), 1N HCl, brine, dried over Na2SO4, and filtered. The filtrate was concentrated in vacuo to provide a golden-yellow oil (18.4 g) which was then distilled in vacuo to afford the title compound as a colorless oil (14.7 g): bp 100-103° C. @ 0.5 torr.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:20](=[O:21])[N:19]([CH3:22])[C:12]2[N:13]=[C:14](SC)[N:15]=[CH:16][C:11]=2[CH:10]=1.[CH:23]([NH2:26])([CH3:25])[CH3:24]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[C:9]1[C:20](=[O:21])[N:19]([CH3:22])[C:12]2[N:13]=[C:14]([NH:26][CH:23]([CH3:25])[CH3:24])[N:15]=[CH:16][C:11]=2[CH:10]=1
Reactant: CSc1ncc2cc(-c3c(Cl)cccc3Cl)c(=O)n(C)c2n1
Reactant: CC(C)N
Product: CC(C)Nc1ncc2cc(-c3c(Cl)cccc3Cl)c(=O)n(C)c2n1

Procedure:
This compound was prepared by a procedure similar to that described in Example 40 starting with 6-(2,6-dichlorophenyl)-8-methyl-2-methylsulfanyl-8H-pyrido[2,3-d]pyrimidin-7-one of Example 37 and isopropylamine; mp 194°-196° C.
Reaction SMILES: S(=O)(=O)(O)O.[CH2:6]([C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:26]=[CH:25][C:23](N)=[CH:22][CH:21]=2)=[N:18][CH:19]=1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13].N([O-])=[O:28].[Na+].[OH-].[Na+]>O>[CH2:6]([C:14]1[CH:15]=[CH:16][C:17]([C:20]2[CH:26]=[CH:25][C:23]([OH:28])=[CH:22][CH:21]=2)=[N:18][CH:19]=1)[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH3:13]
Reactant: CCCCCCCCc1ccc(-c2ccc(N)cc2)nc1
Reactant: O=N[O-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Product: CCCCCCCCc1ccc(-c2ccc(O)cc2)nc1
Temperature: 5 °C
Yield: 35.2 %

Procedure:
10 ml of 3N sulphuric acid were treated while stirring with 1.8 g of p-(5-octyl-2-pyridyl)aniline. The mixture was cooled to 5° C. and then treated dropwise at 0°-5° C. within about 3 minutes with a solution of 0.442 g of sodium nitrite in 2 ml of water. The brown mixture obtained was poured into 100 ml of water and heated to reflux for 30 minutes while stirring. The reaction mixture was subsequently cooled to room temperature, adjusted to about pH 5 with 7 ml of 3N sodium hydroxide solution and extracted once with 200 ml of methylene chloride and once with 100 ml of methylene chloride. The organic phases were washed with 150 ml of dilute sodium chloride solution, dried over sodium sulphate and evaporated in a vacuum. The residue (1.867 g) was separated by chromatography on 250 g of silica gel at 0.4 bar with methylene chloride and methylene chloride/acetone. Recrystallization of the resulting red-brown oil in diethyl ether/hexane at 0° C. gave 0.635 g of p-(5-octyl-2-pyridyl)phenol as beige crystals. Working-up of the mother liquor gave 0.355 g of crude p-(5-octyl-2-pyridyl)phenol as a brown oil.
Reaction SMILES: [CH2:1]([N:8]1[CH:13]2[CH:14]([OH:16])[CH2:15][CH:9]1[CH2:10][C:11](=O)[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC1C=CC(S([CH2:28][N+:29]#[C-])(=O)=O)=CC=1.CC([O-])(C)C.[K+]>COCCOC.CCO>[CH2:1]([N:8]1[CH:13]2[CH:14]([OH:16])[CH2:15][CH:9]1[CH2:10][CH:11]([C:28]#[N:29])[CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C1CC2CC(O)C(C1)N2Cc1ccccc1
Reactant: [C-]#[N+]CS(=O)(=O)c1ccc(C)cc1
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: COCCOC
Solvent: CCO
Product: N#CC1CC2CC(O)C(C1)N2Cc1ccccc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 63.6 %

Procedure:
To a mixture of 8-benzyl-6-hydroxy-8-azabicyclo[3.2.1]octan-3-one (1.2 g) and TosMIC (1.95 g) in a mixture of 20 mL of DME and 0.5 mL of absolute EtOH was added t-BuOK (3.5 g) portionwise while keeping the temperature between 5 and 10° C. The resulting mixture was stirred at room temperature 30 min, and then warmed to 35-40° C. for another 30 minutes. The suspension thus obtained was cooled to room temperature, and the precipitate (TosK) was removed and extracted with DME. The combined DME solutions were concentrated to 3 mL and purified by silica gel chromatography to give 8-benzyl-6-hydroxy-8-azabicyclo[3.2.1]octane-3-carbonitrile 150b (0.8 g).
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[CH:13]=[C:12]([F:14])[C:9]([CH2:10][OH:11])=[C:8]([F:15])[CH:7]=2)[CH2:3][CH2:2]1.[C:16]([O:20][C:21]([N:23]1[CH2:28][CH2:27][N:26]([C:29](Cl)=[O:30])[C@H:25]([CH2:32][CH3:33])[CH2:24]1)=[O:22])([CH3:19])([CH3:18])[CH3:17].[H-].[Na+]>CN(C)C=O>[CH:1]1([CH2:4][O:5][C:6]2[CH:7]=[C:8]([F:15])[C:9]([CH2:10][O:11][C:29]([N:26]3[CH2:27][CH2:28][N:23]([C:21]([O:20][C:16]([CH3:18])([CH3:17])[CH3:19])=[O:22])[CH2:24][C@H:25]3[CH2:32][CH3:33])=[O:30])=[C:12]([F:14])[CH:13]=2)[CH2:3][CH2:2]1
Reactant: OCc1c(F)cc(OCC2CC2)cc1F
Reactant: CC[C@@H]1CN(C(=O)OC(C)(C)C)CCN1C(=O)Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC[C@@H]1CN(C(=O)OC(C)(C)C)CCN1C(=O)OCc1c(F)cc(OCC2CC2)cc1F
Temperature: 25 °C
Reaction time: 5 h
Yield: 70.9 %

Procedure:
A mixture of 4-cyclopropylmethoxy-2,6-difluoro-benzylalcohol (270 mg, 1.26 mM) and (R)-4-chlorocarbonyl-3-ethyl-piperazine-1-carboxylic acid tert-butyl ester (349 mg, 1.26 mM) in dimethylformamide (2 mL) was added slowly to a suspension of sodium hydride (83 mg, 55%, 1.89 mM) in dimethylformamide (2 mL). The mixture was stirred at room temperature for 5 h and partitioned between water and diethylether. Organic phases were pooled, washed with brine and dried with MgSO4 to yield after evaporation a yellow oil (585 mg). This residue was purified by column chromatography (silica gel; n-hexane/ethylacetate gradient) to yield 406 mg (71%) of the product as a yellowish oil. MS (ISP): 477.3 (M+H)+.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[N:4][C:5](=[O:9])[C:6]=1[CH2:7][CH3:8].[H-].[Na+].[CH3:12][CH:13](Cl)[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=1>CN(C)C=O>[CH3:1][C:2]1[NH:3][N:4]([CH:13]([CH3:12])[C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([Cl:21])[CH:15]=2)[C:5](=[O:9])[C:6]=1[CH2:7][CH3:8]
Reactant: CCC1=C(C)N=NC1=O
Reactant: CC(Cl)c1ccc(Cl)c(Cl)c1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCc1c(C)[nH]n(C(C)c2ccc(Cl)c(Cl)c2)c1=O
Temperature: 60 °C
Reaction time: 2 h

Procedure:
25.2 g of 3-methyl-4-ethylpyrazol-5-one were added in portions to a suspension of 10.0 g (0.22 mol) of sodium hydride in 200 ml of absolute dimethylformamide. After the evolution of H2 had ceased, 41.8 g (0.2 mol) of α-methyl-3,4-dichlorobenzyl chloride were added dropwise to the reaction solution. The mixture was then stirred for 2 hours at 60° C, the solvent was distilled off in vacuo and the residue was taken up in water and acidified with dilute acetic acid. The crude product thereby obtained was recrystallized from ethanol.
Reaction SMILES: [NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:2]([C:13]([OH:15])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1.[CH3:23]C(C)([O-])C.[K+].CI>CN(C=O)C>[NH:1]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C@@H:2]([C:13]([OH:15])=[O:14])[CH2:3][C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:23])[CH:5]=1
Reactant: CC(C)(C)[O-]
Reactant: CC(C)(C)OC(=O)N[C@H](Cc1c[nH]c2ccccc12)C(=O)O
Agent: [K+]
Solvent: CI
Solvent: CN(C)C=O
Product: Cn1cc(C[C@@H](NC(=O)OC(C)(C)C)C(=O)O)c2ccccc21
Temperature: 25 °C
Yield: 58.5 %

Procedure:
To a solution of Boc-D-Trp-OH (15.0 g) in DMF (150 ml) were added potassium tert-butoxide (13.8 g) and methyl iodide (10.5 g) under ice-cooling. After stirring under ice-cooling for 30 minutes and at room temperature for 15 minutes, the reaction mixture was poured into ice-cooled 0.24 NHCl, followed by extraction with ethyl acetate. The extract was washed with 5% NaHSO3 and saturated aqueous sodium chloride. Removal of the solvent gave a residue, which was crystallized from diisopropyl ether to afford Boc-D-Trp(CH3)-OH (9.18 g).
Reaction SMILES: [Cl:1][C:2]1[C:7]([CH3:8])=[C:6]([F:9])[CH:5]=[CH:4][CH:3]=1.S(Cl)([Cl:13])(=O)=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>>[Cl:1][C:2]1[C:7]([CH2:8][Cl:13])=[C:6]([F:9])[CH:5]=[CH:4][CH:3]=1
Reactant: Cc1c(F)cccc1Cl
Reactant: O=S(=O)(Cl)Cl
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Product: Fc1cccc(Cl)c1CCl
Reaction time: 3 h

Procedure:
The starting material may be prepared as follows: A mixture of 98 g (0.678 mole) of 6-chloro-2-fluorotoluene, 91.5 g (0.678 mole) of sulfuryl chloride and 0.2 g of dibenzoyl peroxide is stirred for 3 hours at 100°-110° C. and then distilled, affording 6-chloro-2-fluorobenzyl chloride with a boiling point in the range from 78°-82° C.
Reaction SMILES: [C:1]([NH:4][CH2:5][CH2:6][S:7][C:8]1[CH2:14][C@H:13]2[N:10]([C:11](=[O:18])[C@@H:12]2[C@@H:15]([OH:17])[CH3:16])[C:9]=1[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)=[O:20])(=[O:3])[CH3:2].[CH3:32][S:33](Cl)(=[O:35])=[O:34].C(N(CC)CC)C>ClCCl>[C:1]([NH:4][CH2:5][CH2:6][S:7][C:8]1[CH2:14][C@H:13]2[N:10]([C:11](=[O:18])[C@@H:12]2[C@@H:15]([O:17][S:33]([CH3:32])(=[O:35])=[O:34])[CH3:16])[C:9]=1[C:19]([O:21][CH2:22][C:23]1[CH:28]=[CH:27][C:26]([N+:29]([O-:31])=[O:30])=[CH:25][CH:24]=1)=[O:20])(=[O:3])[CH3:2]
Reactant: CS(=O)(=O)Cl
Reactant: CC(=O)NCCSC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@H](C)O)[C@H]2C1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)NCCSC1=C(C(=O)OCc2ccc([N+](=O)[O-])cc2)N2C(=O)[C@H]([C@H](C)OS(C)(=O)=O)[C@H]2C1

Procedure:
p-Nitrobenzyl (5R,6S)-3-(2-acetamidoethylthio)-6-[(S)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (e7) (100 mg) was treated with methanesulphonyl chloride and triethylamine in dichloromethane as described in Example 1. After work-up, evaporation of the dichloromethane solution afforded p-nitrobenzyl (5R,6S)-3-(2-acetamidoethylthio)-6-[(S)-1-methylsulphonyloxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (e8) (112 mg) as a foam; νmax (CH2Cl2) 1785, 1700 sh, 1680, 1525, 1350, 1335 and 1175 cm-1.