Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([CH:9]=[CH:10][N+:11]([O-:13])=[O:12])=[CH:5][CH:4]=1.C(=O)C1C=CC=CC=1.NC1C=CC=CC=1N>>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:9][CH2:10][N+:11]([O-:13])=[O:12])=[CH:7][CH:8]=1
Reactant: COc1ccc(C=C[N+](=O)[O-])cc1
Agent: Nc1ccccc1N
Solvent: O=Cc1ccccc1
Product: COc1ccc(CC[N+](=O)[O-])cc1
Yield: 92 %

Procedure:
227 A) 4-Methoxy-b-nitrostyrene (25.0 g, 0.15 mole) was reacted with benzaldehyde (19.1 g, 0.18 mole) and 1,2-diaminobenzene (19.8 g, 0.18 mole) according to the procedure of Chikashita et. al. (Synth. Commun. 1985, 15 (6), 527) to yield methoxy-4-(2-nitroethyl)benzene (25.0 g, 93%) as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[SH:8].[Cl:9][C:10]1[CH:19]=[C:18]([CH2:20]Cl)[C:13]2[O:14][CH2:15][O:16][CH2:17][C:12]=2[CH:11]=1.C(=O)([O-])[O-].[K+].[K+]>C(O)C.C(OCC)(=O)C>[ClH:9].[Cl:9][C:10]1[CH:19]=[C:18]([CH2:20][S:8][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=2[NH2:1])[C:13]2[O:14][CH2:15][O:16][CH2:17][C:12]=2[CH:11]=1
Reactant: Nc1ccccc1S
Reactant: ClCc1cc(Cl)cc2c1OCOC2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CCO
Product: Cl
Product: Nc1ccccc1SCc1cc(Cl)cc2c1OCOC2
Reaction time: 18 h

Procedure:
2-aminothiophenol (1.25 g, 10 mmol), 6-chloro-8-(chloromethyl)-4H-1,3-benzodioxine (2.17 g, 10 mmol) and potassium carbonate (4.10 g, 30 mmol) were combined in absolute ethanol (100 mL) and stirred 18 h. Dilute with ethyl acetate and wash with saturated sodium bicarbonate solution then brine. The solution was dried over sodium sulfate and the solvent removed in vacuo. The residue was dissolved in methanol and treated with MP BH4− resin (Argonaut 3.16 mmol/g) and potassium carbonate for 48 h. The mixture was filtered and the solvent removed in vacuo. The resulting oil was dissolved in dichloromethane and passed through a 5 g plug of silica gel. The solvent was removed in vacuo and the residue was precipitated from diethyl ether with a solution of hydrogen chloride in dioxane to give the product as an off white powder, 2.52 g (74%). MS (ESI+) for C15H14ClNO2S m/z 308 (M+H)+.
Reaction SMILES: Cl.[NH2:2][CH:3]1[C:9](=[O:10])[N:8]([CH2:11][CH2:12][O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:7]2[CH:21]=[CH:22][CH:23]=[CH:24][C:6]=2[N:5]([CH2:25][C:26]([F:29])([F:28])[F:27])[CH2:4]1.[OH:30][C:31]([CH3:46])([C:35]([NH:37][CH2:38][C:39]([F:45])([F:44])[C:40]([F:43])([F:42])[F:41])=[O:36])[C:32](O)=[O:33].ON1C2C=CC=CC=2N=N1>>[CH2:14]([O:13][CH2:12][CH2:11][N:8]1[C:9](=[O:10])[CH:3]([NH:2][C:32](=[O:33])[C:31]([OH:30])([CH3:46])[C:35]([NH:37][CH2:38][C:39]([F:44])([F:45])[C:40]([F:41])([F:43])[F:42])=[O:36])[CH2:4][N:5]([CH2:25][C:26]([F:29])([F:28])[F:27])[C:6]2[CH:24]=[CH:23][CH:22]=[CH:21][C:7]1=2)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1
Reactant: CC(O)(C(=O)O)C(=O)NCC(F)(F)C(F)(F)F
Reactant: NC1CN(CC(F)(F)F)c2ccccc2N(CCOCc2ccccc2)C1=O
Agent: Cl
Agent: On1nnc2ccccc21
Product: CC(O)(C(=O)NCC(F)(F)C(F)(F)F)C(=O)NC1CN(CC(F)(F)F)c2ccccc2N(CCOCc2ccccc2)C1=O

Procedure:
In an analogous manner to that described in Example 1e), the condensation of 3-amino-1-(2-benzyloxy-ethyl)-5-(2,2,2-trifluoro-ethyl)-1,3,4,5-tetrahydro-benzo[b][1,4]diazepin-2-one hydrochloride and (RS)-2-hydroxy-2-methyl-N-(2,2,3,3,3-pentafluoro-propyl)-malonamic acid with 1-hydroxy-benzotriazole and N-(3-dimethylaminpropyl)-N′-ethyl-carbodiimide hydrochloride as the condensating agents yielded a mixture of the four epimeric title compounds as a white foam; MS (m/e): 641 (M+H)+.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[Cl:5][C:6]1[CH:14]=[CH:13][C:9]([C:10](Cl)=[O:11])=[CH:8][CH:7]=1.[CH2:15]([C:22]1[C:27]([Cl:28])=[CH:26][C:25]([N+:29]([O-:31])=[O:30])=[CH:24][C:23]=1[Cl:32])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1.Cl>ClCCl.C(Cl)(Cl)Cl>[Cl:5][C:6]1[CH:14]=[CH:13][C:9]([C:10]([C:19]2[CH:20]=[CH:21][C:16]([CH2:15][C:22]3[C:27]([Cl:28])=[CH:26][C:25]([N+:29]([O-:31])=[O:30])=[CH:24][C:23]=3[Cl:32])=[CH:17][CH:18]=2)=[O:11])=[CH:8][CH:7]=1
Reactant: O=C(Cl)c1ccc(Cl)cc1
Reactant: O=[N+]([O-])c1cc(Cl)c(Cc2ccccc2)c(Cl)c1
Agent: Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: ClC(Cl)Cl
Product: O=C(c1ccc(Cl)cc1)c1ccc(Cc2c(Cl)cc([N+](=O)[O-])cc2Cl)cc1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
In 15 ml of dichloromethane was suspended 1.30 g of AlCl3, and a solution of 1.43 g of 4-chlorobenzoyl chloride in 3 ml of dichloromethane was added to the suspension for a period of 30 minutes. A solution of 2.00 g of 4-benzyl-3,5-dichloronitrobenzene in 2 ml of dichloromethane was added for a period of 15 minutes, and the reaction mixture was refluxed for 22 hours. The reaction mixture was poured into 25 ml of ice-water, and 30 ml of chloroform and 3 ml of conc. hydrochloric acid were added. The resulting mixture was stirred for 15 minutes at a room temperature, and the organic layer was separated, washed with water and saturated aqueous sodium bicarbonate solution, dried and concentrated to quantitatively give the above-identified compound as oil.
Reaction SMILES: [N+]([C:4]1[CH:11]=[CH:10][CH:9]=[C:6]([C:7]#[N:8])[C:5]=1[C:12]#[N:13])([O-])=O.[C:14]1([C:16](=[CH:18][CH:19]=[CH:20][CH:21]=1)O)[OH:15].[C:22](=[O:25])([O-])[O-].[K+].[K+].O>CS(C)=O>[C:12]([C:5]1[C:6]([C:7]#[N:8])=[CH:9][CH:10]=[CH:11][C:4]=1[O:15][C:14]1[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=1[O:25][C:22]1[CH:11]=[CH:10][CH:9]=[C:6]([C:7]#[N:8])[C:5]=1[C:12]#[N:13])#[N:13]
Reactant: Oc1ccccc1O
Reactant: N#Cc1cccc([N+](=O)[O-])c1C#N
Reactant: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CS(C)=O
Product: N#Cc1cccc(Oc2ccccc2Oc2cccc(C#N)c2C#N)c1C#N
Temperature: 25 °C
Reaction time: 26 h

Procedure:
The same apparatus as was used in Example 1 was also used in this example. 3 g (0.0173 moles) of 3-nitrophthalonitrile, was dissolved in 15 ml of anhydrous dimethyl sulphoxide in the three-necked flask. 0.95 g (0.00863 moles) of catechol and 2 g of potassium carbonate were added to the reaction mixture. The mixture was stirred at room temperature with a stream of dry, oxygen-free nitrogen passing through the flask for 26 hours. The product was isolated by pouring the reaction mixture into 300 ml of water. The resultant solid precipitate was filtered and washed until the effluent was neutral. The product (which was an off-white powder) was recrystallized from methanol/acetonitrile (20/80) to yield off-white crystals of 1,2-bis-(2,3-dicyanophenoxy) benzene having the formula: ##STR9## The melting point was 158°-159° C. The elemental analysis for C22H10N4O2 was calc.: C, 72.92%; H, 2.76%; N, 15.67%; found: C, 72.57%; H, 2.72%; N, 15.43%.
Reaction SMILES: [C:1]1([CH:7]([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[N:8]2[CH2:11][C:10]([CH3:17])(OS(C)(=O)=O)[CH2:9]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C-:24]#[N:25].[Na+]>CN(C)C=O>[C:24]([C:10]1([CH3:17])[CH2:11][N:8]([CH:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH2:9]1)#[N:25]
Reactant: CC1(OS(C)(=O)=O)CN(C(c2ccccc2)c2ccccc2)C1
Reactant: [C-]#N
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC1(C#N)CN(C(c2ccccc2)c2ccccc2)C1
Reaction time: 6 h
Yield: 82.9 %

Procedure:
33.1 g (100 mmol) of 1-diphenylmethyl-3-methyl-3-methylsulphonyloxyazetidine are added to a suspension of sodium cyanide (11 g, 225 mmol) in dimethylformamide (90 ml) and the mixture is stirred at 65°-70° C. for 6 hours. It is cooled and poured onto a water/ice mixture, the product is filtered off, washed with water and dried at 50° C. and 21.75 g (83%) of 3-cyano-1-diphenylmethyl-3-methylazetidine, melting point 86°-88° C., are obtained.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH:9]([S:12]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[CH:16]=2)(=[O:14])=[O:13])[CH2:10]Cl)=[CH:4][CH:3]=1.C(N(CC)CC)C>O1CCCC1.C(OCC)C>[N+:21]([C:17]1[CH:16]=[C:15]([S:12]([C:9]([S:8][C:5]2[CH:4]=[CH:3][C:2]([Br:1])=[CH:7][CH:6]=2)=[CH2:10])(=[O:14])=[O:13])[CH:20]=[CH:19][CH:18]=1)([O-:23])=[O:22]
Reactant: O=[N+]([O-])c1cccc(S(=O)(=O)C(CCl)Sc2ccc(Br)cc2)c1
Solvent: CCN(CC)CC
Solvent: CCOCC
Solvent: C1CCOC1
Product: C=C(Sc1ccc(Br)cc1)S(=O)(=O)c1cccc([N+](=O)[O-])c1
Yield: 48.3 %

Procedure:
2-Chloro-1-(m-nitrophenylsulfonyl)ethyl p-bromophenyl sulfide (27.1 g, 62.1 mmoles) was dissolved in 125 ml of tetrahydrofuran. The solution was diluted with 125 ml of diethyl ether and treated with 8.65 ml (6.3 g, 62.3 mmoles) of triethylamine. After one hour the mixture was filtered to remove 7.52 g (88%) of triethylamine hydrochloride, m.p. 255°-258°. Removal of solvent from the filtrate gave a yellow oil which crystallized upon scraping. Recrystallization from 25 ml of ethyl acetate and 10 ml of pentane gave 12 g (48%) of product m.p. 109°-111°.
Reaction SMILES: [CH3:1][C:2]1[N:3]=[C:4]([C:7]([O:9]C)=O)[S:5][CH:6]=1.O.[NH2:12][NH2:13]>CO>[CH3:1][C:2]1[N:3]=[C:4]([C:7]([NH:12][NH2:13])=[O:9])[S:5][CH:6]=1
Reactant: COC(=O)c1nc(C)cs1
Reactant: NN
Solvent: CO
Solvent: O
Product: Cc1csc(C(=O)NN)n1
Reaction time: 1.5 h

Procedure:
To a solution of methyl 4-methyl-2-thiazole carboxylate (step a, 2.1 g) in methanol (20 ml) was added hydrazine hydrate (3.2 ml) dropwise over 30 mins. The reaction mixture was stirred for 1.5 hours and the precipitate filtered off to yield the title compound as a white solid (1.6 g). 1H NMR (250 MHz, DMSO) 8 2.64 (3H, s), 4.82 (2H, bs), 7.79 (1H, s), 10.25 (1H, bs).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[C:6]([C:8](=[C:11]([S:14][CH3:15])SC)[C:9]#[N:10])=O.N[N:17]=[CH:18][NH:19][C:20](=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.C([N:30](CC)CC)C>CN(C=O)C>[C:9]([C:8]1[C:6]([C:2]2[O:1][CH:5]=[CH:4][CH:3]=2)=[N:17][C:18]([NH:19][C:20](=[O:27])[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[N:30][C:11]=1[S:14][CH3:15])#[N:10]
Reactant: NN=CNC(=O)c1ccccc1
Reactant: CSC(SC)=C(C#N)C(=O)c1ccco1
Reactant: CCN(CC)CC
Solvent: CN(C)C=O
Product: CSc1nc(NC(=O)c2ccccc2)nc(-c2ccco2)c1C#N
Temperature: 25 °C
Yield: 56.9 %

Procedure:
Following the method of Rudorf and Augustin (J. Prakt. Chem. 1978, 320, 576), a solution of 250 mg (1.04 mmol) 2-(furan-2-carbonyl)-3,3-bis-methylsulfanyl-acrylonitrile, 205 mg (1.25 mmol) N-(aminoiminomethyl)benzamide and 0.36 ml (2.61 mmol) triethylamine in 5 ml DMF was heated at reflux for 6 h. The reaction mixture was then cooled to room temperature and partitioned between ethyl acetate and water. The phases were separated and the organic phase dried over sodium sulfate and concentrated in vacuo. Chromatography (hexane then ethyl acetate/hexane 1/1) afforded 199 mg (57%) N-(5-cyano-4-furan-2-yl-6-methylsulfanyl-pyrimidin-2-yl)-benzamide as an off-white amorphous solid. ES-MS m/e (%): 359 (M+Na+, 36), 337 (M+H+, 100).
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][O:9][C:10]1[CH:11]=[C:12]([C:18]2[N:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]([OH:28])=O)=[CH:20][CH:19]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH3:17].[NH2:29][C:30]1[CH:35]=[C:34]([C:36]2[S:37][CH:38]=[CH:39][CH:40]=2)[CH:33]=[CH:32][C:31]=1[NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45].CN([P+](ON1N=NC2C=CC=CC1=2)(N(C)C)N(C)C)C.F[P-](F)(F)(F)(F)F>N1C=CC=CC=1>[CH3:8][O:9][C:10]1[CH:11]=[C:12]([C:18]2[N:23]=[CH:22][C:21](/[CH:24]=[CH:25]/[C:26]([NH:29][C:30]3[CH:35]=[C:34]([C:36]4[S:37][CH:38]=[CH:39][CH:40]=4)[CH:33]=[CH:32][C:31]=3[NH:41][C:42](=[O:48])[O:43][C:44]([CH3:46])([CH3:45])[CH3:47])=[O:28])=[CH:20][CH:19]=2)[CH:13]=[CH:14][C:15]=1[O:16][CH3:17]
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1N
Reactant: COc1ccc(-c2ccc(/C=C/C(=O)O)cn2)cc1OC
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: O=C(O)C(F)(F)F
Solvent: c1ccncc1
Product: COc1ccc(-c2ccc(/C=C/C(=O)Nc3cc(-c4cccs4)ccc3NC(=O)OC(C)(C)C)cn2)cc1OC
Yield: 100.4 %

Procedure:
A solution of acid 40 (0.10 g, 0.25 mmol), amine 4 (72.7 mg, 0.25 mmol) and BOP reagent (0.133 g, 3.0 mmol) in pyridine (2 mL) was stirred 18 h at room temperature. The reaction mixture was concentrated and the residue was purified by flash chromatography (eluent: 1:1 hexane:AcOEt) to give title compound 41 (0.14 g, 61% yield).
Reaction SMILES: [CH3:1][O:2][C@@H:3]1[C@:8]2([O:10][CH2:9]2)[C@H:7](/[CH:11]=[CH:12]/[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[O:6][CH2:5][C@@H:4]1[CH3:20].[CH:21]1[N-:25][CH:24]=[N:23][CH:22]=1.[Na+]>CN(C)C=O.O>[N:23]1([CH2:9][C@:8]2([OH:10])[C@@H:3]([O:2][CH3:1])[C@@H:4]([CH3:20])[CH2:5][O:6][C@H:7]2/[CH:11]=[CH:12]/[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19])[CH:22]=[CH:21][N:25]=[CH:24]1
Reactant: CCCCCCC/C=C/[C@@H]1OC[C@H](C)[C@H](OC)[C@@]12CO2
Reactant: c1c[n-]cn1
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: CCCCCCC/C=C/[C@@H]1OC[C@H](C)[C@H](OC)[C@@]1(O)Cn1ccnc1
Temperature: 25 °C
Reaction time: 15 h
Yield: 78.7 %

Procedure:
A mixture of (3S,4S,7S,8S)-8-methoxy-7-methyl-4-[(E)-1-nonenyl]-1,5-dioxaspiro[2,5]octane (4.2 mg) and imidazole sodium derivative (14.0 mg) in dry N,N-dimethylformamide (0.5 ml) was stirred for 15 hours at room temperature. The reaction mixture was diluted with water. The mixture was extracted with dietyl ether, the combined ethereal extracts were washed with brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification of the residue by preparative thin layer chromatography (ethyl acetate as an eluent) gave (2S,3S,4S, 5S)-3-(1H-imidazol-1-ylmethyl)-4-methoxy-5-methyl-2-[(E)-1-nonenyl]tetrahydro-2H-pyran-3-ol (4.1 mg, y. 79%) as colorless oil; EI-MS: m/z 351 (M+); 1H-NMR (CDCl3)d: 0.88 (3H,t,J=8 Hz), 1.10 (3H,d,J=7 Hz), 1.2-1.5 (10H,m), 2.1 (3H,m), 2.39 (1H,br.s, --OH), 2.93 (1H,d,J=5 Hz), 3.39 (3H,s), 3.40 (1H,dd,J=3 & 12 Hz), 3.61 (1H,d,J=8 Hz), 3.76 (1H,dd,J=4 & 12 Hz), 3.96 (1H,d,J=14 Hz), 4.13 (1H,d,J=14 Hz), 5.87 (2H,m), 6.91 (1H,s), 7r14(1H,s), 7.46 (1H,s).
Reaction SMILES: NC[C:3]1[CH:4]=[C:5]([CH:36]=[CH:37][CH:38]=1)[CH2:6][N:7]1[CH:11]=[C:10]([C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH2:14][CH2:15][CH2:16][N:17]3[C:22](=[O:35])[CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[C:28]=2[CH3:34])[CH:9]=[N:8]1.BrC1C=[N:42]N(CC2C=C(C=CC=2)CNC(=O)OC(C)(C)C)C=1.BrC1C=CC=C2C=1CCCN2C(=O)CCCOC1C=CC=C(C)C=1C.CC1C(C)=CC=CC=1OCCCC(N1C2C(=C(B3OC(C)(C)C(C)(C)O3)C=CC=2)CCC1)=O.CC1(C)C(C)(C)OB(C2C=NN(CC3C=C(NC(=O)OC(C)(C)C)C=CC=3)C=2)O1>>[NH2:42][C:3]1[CH:4]=[C:5]([CH:36]=[CH:37][CH:38]=1)[CH2:6][N:7]1[CH:11]=[C:10]([C:12]2[CH:21]=[CH:20][CH:19]=[C:18]3[C:13]=2[CH2:14][CH2:15][CH2:16][N:17]3[C:22](=[O:35])[CH2:23][CH2:24][CH2:25][O:26][C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([CH3:33])[C:28]=2[CH3:34])[CH:9]=[N:8]1
Reactant: CC(C)(C)OC(=O)NCc1cccc(Cn2cc(Br)cn2)c1
Reactant: Cc1cccc(OCCCC(=O)N2CCCc3c(-c4cnn(Cc5cccc(CN)c5)c4)cccc32)c1C
Agent: CC(C)(C)OC(=O)Nc1cccc(Cn2cc(B3OC(C)(C)C(C)(C)O3)cn2)c1
Agent: Cc1cccc(OCCCC(=O)N2CCCc3c(B4OC(C)(C)C(C)(C)O4)cccc32)c1C
Agent: Cc1cccc(OCCCC(=O)N2CCCc3c(Br)cccc32)c1C
Product: Cc1cccc(OCCCC(=O)N2CCCc3c(-c4cnn(Cc5cccc(N)c5)c4)cccc32)c1C

Procedure:
The title compound was prepared using a procedure analogous to 1-(5-(1-(3-(aminomethyl)benzyl)-1H-pyrazol-4-yl)-3,4-dihydroquinolin-1(2H)-yl)-4-(2,3-dimethylphenoxy)butan-1-one except that tert-butyl 3-((4-bromo-1H-pyrazol-1-yl)methyl)benzylcarbamate was replaced by 1-(5-bromo-3,4-dihydroquinolin-1(2H)-yl)-4-(2,3-dimethylphenoxy)butan-1-one and 4-(2,3-dimethylphenoxy)-1-(5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-3,4-dihydroquinolin-1(2H)-yl)butan-1-one was replaced by tert-butyl 3-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazol-1-yl)methyl)phenylcarbamate. LCMS, [M+H]+=495.4.
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([S:10]([NH2:13])(=[O:12])=[O:11])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[C:14]([C:17]1[CH:24]=[CH:23][C:20]([CH:21]=O)=[CH:19][CH:18]=1)([OH:16])=[O:15].CC1C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[C:14]([C:17]1[CH:24]=[CH:23][C:20]([CH:21]=[N:13][S:10]([C:6]2[CH:7]=[CH:8][CH:9]=[C:4]([N+:1]([O-:3])=[O:2])[CH:5]=2)(=[O:11])=[O:12])=[CH:19][CH:18]=1)([OH:16])=[O:15]
Reactant: NS(=O)(=O)c1cccc([N+](=O)[O-])c1
Reactant: O=Cc1ccc(C(=O)O)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: Cc1ccccc1
Product: O=C(O)c1ccc(C=NS(=O)(=O)c2cccc([N+](=O)[O-])c2)cc1

Procedure:
In a similar manner to Example 2, 2.02 g (10 mmol) of 3-nitrobenzenesulfonamide, 1.50 g (10 mmol) of 4-carboxybenzaldehyde and 20 mg of TsOH in 150 mL of toluene were heated for 5 hours to yield 3.23 g (97%) of SULF-6 as a white powder: IR (Nujol) 3200-2500 (br), 1685, 1554, 1379, 1352, 1165 cm-1 ; 1H NMR (DMSO-d6, TMS ext std) δ 9.24 (s, 1), 8.47 (s, 1), 7.9-6.9 (m, 7).
Reaction SMILES: [C-:1]#[N:2].[K+].Cl.[CH3:5][NH:6][CH3:7].[CH3:8][C:9](=O)[CH2:10][CH2:11][CH2:12][CH3:13]>O>[CH3:8][C:9]([N:6]([CH3:7])[CH3:5])([CH2:10][CH2:11][CH2:12][CH3:13])[C:1]#[N:2]
Reactant: CNC
Reactant: [C-]#N
Reactant: CCCCC(C)=O
Agent: Cl
Agent: [K+]
Solvent: O
Product: CCCCC(C)(C#N)N(C)C
Reaction time: 24 h

Procedure:
A solution of potassium cyanide (34.20 g.,) in water (75 ml.) was added dropwise to a stirred solution of dimethylamine hydrochloride (40.8 g.,) and hexane-2-one (50 g., 0.5 mole) in water (60 ml.) cooled in an ice-water bath. The mixture was vigorously stirred for 24 hrs., diluted with water (200 ml.) and extracted with ether (4 × 200 ml.). The combined ether extracts were washed with water (4 × 200 ml.), dried (Na2SO4) and evaporated to leave a colourless oil which was distilled at 12 mm. to give a colourless oil which when distilled gave 2-methyl-2-dimethylamino-hexanenitrile as a colourless oil (51.547 g., 67%, b.p. 92°/12 mm).
Reaction SMILES: S(OOS([O-])(=O)=O)([O-])(=O)=O.[NH4+].[NH4+].[CH3:13][N:14]([CH2:16][C:17]1[CH:22]=[CH:21][N:20]=[CH:19][CH:18]=1)[CH3:15].[CH3:23][OH:24].S(=O)(=O)(O)O>O>[CH3:13][N:14]([CH2:16][C:17]1[CH:22]=[CH:21][N:20]=[C:19]([CH2:23][OH:24])[CH:18]=1)[CH3:15]
Reactant: CO
Reactant: CN(C)Cc1ccncc1
Agent: O=S(=O)(O)O
Agent: O=S(=O)([O-])OOS(=O)(=O)[O-]
Agent: [NH4+]
Solvent: O
Product: CN(C)Cc1ccnc(CO)c1

Procedure:
Ammonium persulphate (102.7 g) in water (200 ml) was added over 40 minutes to a refluxing solution of 4-dimethylaminomethylpyridine (40.86 g), methanol (450 ml), water (210 ml) and concentrated sulphuric acid (30 ml). The resulting solution was refluxed for 2 hours, water (300 ml) was added and the methanol was distilled off. The cooled solution was basified and extracted with chloroform to give 4-dimethylaminomethyl-2-hydroxymethylpyridine (19.65 g) b.p. 92°-120°/0.06 mm Hg.
Reaction SMILES: [BH4-].[Na+].[O:3]1[C@H:5]2[C:6](=[O:37])[CH2:7][C@H:8]3[C@:29]([CH3:30])([C@@H:4]12)[C@@H:28]1[C@H:11]([C@H:12]2[C@:25]([CH3:31])([CH2:26][CH2:27]1)[C@@H:15]([C@H:16]([CH3:24])[CH2:17][CH2:18][CH2:19][C:20]([OH:23])([CH3:22])[CH3:21])[CH2:14][CH2:13]2)[CH2:10][C@H:9]3[O:32][S:33]([CH3:36])(=[O:35])=[O:34].[BH4-].[Li+].O>O1CCCC1>[OH:3][C@@H:4]1[C@@:29]2([CH3:30])[C@@H:8]([C@H:9]([O:32][S:33]([CH3:36])(=[O:35])=[O:34])[CH2:10][C@@H:11]3[C@@H:28]2[CH2:27][CH2:26][C@@:25]2([CH3:31])[C@H:12]3[CH2:13][CH2:14][C@@H:15]2[C@H:16]([CH3:24])[CH2:17][CH2:18][CH2:19][C:20]([OH:23])([CH3:22])[CH3:21])[CH2:7][CH:6]([OH:37])[CH2:5]1
Reactant: C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3C[C@@H](OS(C)(=O)=O)[C@H]4CC(=O)[C@@H]5O[C@@H]5[C@]4(C)[C@H]3CC[C@]12C
Agent: [BH4-]
Agent: [Li+]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: C[C@H](CCCC(C)(C)O)[C@H]1CC[C@H]2[C@@H]3C[C@@H](OS(C)(=O)=O)[C@H]4CC(O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Reaction time: 0.42 h
Yield: 10.9 %

Procedure:
To 1-molar diborane-tetrahydrofuran complex (not stabilized with sodium borohydride, 157 ml) cooled in an ice bath, was added dropwise over about 25 minutes a solution of 1α,2α-epoxy-6β-methylsulfonyloxy-5α-cholestan-25-ol-3-one (20.0 g, 0.392 mole), in tetrahydrofuran (100 ml) with stirring under an atmosphere of nitrogen. After the addition was complete, the solution was stirred for about 25 minutes. Lithium borohydride (3.40 g, 0.155 mole) was added in 1 portion to the reaction mixture, with stirring. The suspension was stirred in an ice bath for about 6 hours and then stored in a refrigerator (ca. 3° C) overnight. Water (200 ml) was added cautiously to the reaction mixture cooled in an ice bath. An additional 200 ml of water was added to the turbid solution and the solution was extracted with methylene chloride. The layers were separated and the organic phase was washed successively with water and saturated sodium chloride solution, dried over anhydrous sodium sulfate and filtered. Evaporation of the filtrate gave 22 g of 1α,25-dihydroxy-6β-methylsulfonyloxy-5α-cholestan-3-ol as a white foam.
Reaction SMILES: [Cl:1][C:2]1[C:3]([CH3:16])=[CH:4][C:5]([F:15])=[C:6]([CH:14]=1)[C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8].[Br:17]N1C(=O)CCC1=O.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.C(N(C(C)C)CC)(C)C.P([O-])(OCC)OCC>ClCCCl>[Br:17][CH2:16][C:3]1[C:2]([Cl:1])=[CH:14][C:6]([C:7]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[O:8])=[C:5]([F:15])[CH:4]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: Cc1cc(F)c(C(=O)NS(C)(=O)=O)cc1Cl
Agent: CCOP([O-])OCC
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: CS(=O)(=O)NC(=O)c1cc(Cl)c(CBr)cc1F
Reaction time: 5 h
Yield: 43.9 %

Procedure:
To a suspension of 5-chloro-2-fluoro-4-methyl-N-(methylsulfonyl)benzamide (Preparation 22, 118 g, 0.45 mol) in 1,2-dichloroethane (1.25 L) were added N-bromosuccinimide (91 g, 0.51 mol) and benzoyl peroxide (5 g, 20 mmol) and the mixture was heated at reflux for 18 hours. N-bromosuccinimide (30 g, 0.17 mol) was added and the mixture was heated for further 24 hours. N-bromosuccinimide (20 g, 0.11 mol) was then added and the mixture heated for another 3 hours, then cooled and washed with water (1 L) and aqueous sodium thiosulphate (0.5 M, 200 mL). The organic layer was washed with water (500 mL), dried over sodium sulfate and evaporated. The resulting crude tan solid was dissolved in EtOAc (1 L), diisopropylethylamine (130 mL, 0.75 mol) and diethyl phosphite (27.6 g, 0.2 mol) were added and the mixture was stirred for 5 hours under a nitrogen atmosphere. The reaction mixture was then washed with aqueous hydrochloric acid (2 M, 1 L), dried over magnesium sulfate and evaporated to yield a dark solid, which was triturated with diethyl ether (200 mL) to afford the title compound as a tan solid (68 g). The filtrate was purified by silica gel chromatography eluting with 10% EtOAc and 1% acetic acid in DCM, followed by recrystallization with MeCN (130 mL) to afford a second crop of the title compound.
Reaction SMILES: Br[CH2:2][CH2:3][CH2:4][Si:5]([CH3:35])([CH3:34])[CH2:6][CH2:7][C:8]1[C:20]2[CH2:19][N:18]3[C:13](=[CH:14][C:15]4[C@:25]([CH2:27][CH3:28])([OH:26])[C:24](=[O:29])[O:23][CH2:22][C:16]=4[C:17]3=[O:21])[C:12]=2[N:11]=[C:10]2[CH:30]=[CH:31][CH:32]=[CH:33][C:9]=12.C(=O)([O-])[O-].[K+].[K+].CC(O)(C)C.[CH3:47][NH:48][CH3:49]>O.O1CCCC1>[CH3:47][N:48]([CH3:49])[CH2:2][CH2:3][CH2:4][Si:5]([CH3:35])([CH3:34])[CH2:6][CH2:7][C:8]1[C:20]2[CH2:19][N:18]3[C:13](=[CH:14][C:15]4[C@:25]([CH2:27][CH3:28])([OH:26])[C:24](=[O:29])[O:23][CH2:22][C:16]=4[C:17]3=[O:21])[C:12]=2[N:11]=[C:10]2[CH:30]=[CH:31][CH:32]=[CH:33][C:9]=12
Reactant: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccccc1c2CC[Si](C)(C)CCCBr
Reactant: CNC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)(C)O
Solvent: C1CCOC1
Solvent: O
Product: CC[C@@]1(O)C(=O)OCc2c1cc1n(c2=O)Cc2c-1nc1ccccc1c2CC[Si](C)(C)CCCN(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 56 %

Procedure:
A mixture of Compound 11 (50 mg) and potassium carbonate (37 mg) in deionized water (1 mL) was stirred at room temperature for 30 min. To the resulting mixture, t-BuOH (1 mL) and 2 molar dimethylamine in tetrahydrofuran (0.14 mL) were added and stirred at room temperature for 24 hours. Finally, the reaction mixture was concentrated under vacuum and the resulting residue was dissolved in a mixture of acetic acid (10 mL) and trifluoroacetic acid (1 mL) and stirred at room temperature for 8 hours. The crude material was obtained by concentrating the acetic acid solution under vacuum and the residue was partitioned between 7% aqueous NaHCO3 solution (5 mL) and chloroform (2×10 mL). The combined organic layer was dried and concentrated and the residue was eluted on a silica gel column using 10% ethanol in dichloromethane to obtain the required product in 56% yield (26 mg).