Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [O-2:1].[Mg+2].[O-2].[Ca+2:4].[C:5](=[O:7])=[O:6]>O>[C:5](=[O:1])([OH:7])[O-:6].[Ca+2:4].[C:5](=[O:1])([OH:7])[O-:6]
Reactant: [O-2]
Reactant: O=C=O
Agent: [Ca+2]
Agent: [Mg+2]
Solvent: O
Product: O=C([O-])O

Procedure:
The said calcination process is to calcine the minerals at 700˜1000° C. for 1˜5 hours. The said hydration process is to add water into the magnesium oxide and/or calcium oxide obtained from the calcination to carry out hydration, the hydration temperature is 50˜95° C., the hydration time is 0.5˜5 hours, and the weight ratio of water to magnesium oxide and/or calcium oxide is 1˜5:1, and subsequently, water is further added to prepare slurry at the weight ratio of water to magnesium oxide and/or calcium oxide of 10˜200:1. The said carbonation process is performed after the hydration, carbon dioxide is pumped into the slurry to carry out carbonation, the temperature is controlled at 0˜50° C., the reaction time is 0.1˜5 hours. And after filtration, pure magnesium bicarbonate and/or calcium bicarbonate solution is obtained.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:17]=[CH:16][N+:15]([O-:18])=[CH:14][CH:13]=3)[N:9]=[C:10](I)[C:3]=12.[O:19]([C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(COC)OC.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C:12]3[CH:17]=[CH:16][N+:15]([O-:18])=[CH:14][CH:13]=3)[N:9]=[C:10]([C:29]3[CH:30]=[CH:31][C:26]([O:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[CH:27][CH:28]=3)[C:3]=12
Reactant: Nc1ncnc2c1c(I)nn2-c1cc[n+]([O-])cc1
Reactant: OB(O)c1ccc(Oc2ccccc2)cc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: Nc1ncnc2c1c(-c1ccc(Oc3ccccc3)cc1)nn2-c1cc[n+]([O-])cc1
Yield: 87.5 %

Procedure:
A suspension of 4-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)-1-pyridiniumolate (0.140 g, 0.00040 mol) in dimethoxyethane (7 mL) and water (15 mL) was reacted with 4-phenoxyphenylboronic acid (0.093 g, 0.00043 mol), sodium carbonate (0.105 g, 0.00099 mol) and tetrakis(triphenylphosphine)palladium (O) (0.046 g, 0.00004 mol) at 80° C. for 18 hours. The solid was filtered to give 4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate (0.138 g, 0.00035 mol) as a brown solid. A portion (0.040 g, 0.00010 mol) was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 A, 25 cm; 40% isocratic for five minutes, then 40%-100% acetonitrile-0.1M ammonium acetate over 30 min, 21 ml/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give the product 4-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-pyridiniumolate as a white solid (0.013 g, 0.00003 mol).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[O:4][CH2:5][C:6](=[O:12])[C:7]([CH3:11])([CH3:10])[CH2:8][F:9].[Br:18]Br>C(Cl)(Cl)Cl>[Br:18][CH:5]([O:4][C:3]1[CH:13]=[CH:14][C:15]([Cl:17])=[CH:16][C:2]=1[Cl:1])[C:6](=[O:12])[C:7]([CH3:11])([CH3:10])[CH2:8][F:9]
Reactant: CC(C)(CF)C(=O)COc1ccc(Cl)cc1Cl
Reactant: BrBr
Solvent: ClC(Cl)Cl
Product: CC(C)(CF)C(=O)C(Br)Oc1ccc(Cl)cc1Cl
Reaction time: 0.5 h
Yield: 100 %

Procedure:
244.6 g (0.88 mol) of crude 1-(2,4-dichloro-phenoxy)-3,3-dimethyl-4-fluoro-2-butanone were dissolved in 700 ml of chloroform, and 46 ml of bromine were added dropwise at 30° C. at a rate such that decolorization continuously occurred. When the addition had ended, the mixture was subsequently stirred for 30 minutes and then concentrated by distilling off the chloroform in vacuo. 315 g (100% of theory) of 1-bromo-1-(2,4-dichlorophenoxy)-3,3-dimethyl-4-fluoro-2-butanone were obtained as a viscous oil which could be further reacted in crude form.
Reaction SMILES: O[C:2]1[N:3]=[C:4]2[NH:11][C:10]([CH3:13])([CH3:12])[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1.P(Cl)(Cl)([Cl:16])=O.[OH-].[Na+]>>[Cl:16][C:2]1[N:3]=[C:4]2[NH:11][C:10]([CH3:13])([CH3:12])[CH2:9][N:5]2[C:6](=[O:8])[CH:7]=1
Reactant: CC1(C)Cn2c(nc(O)cc2=O)N1
Reactant: O=P(Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Product: CC1(C)Cn2c(nc(Cl)cc2=O)N1
Temperature: 120 °C

Procedure:
4.5 g of 7-hydroxy-2,2-dimethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one and 35 ml of phosphorus oxychloride are introduced into a round-bottomed flask. The resulting mixture is then heated at 120° C. for three hours. After cooling, the reaction mixture is concentrated to dryness under reduced pressure. Ice is added to the residue obtained, and then concentrated sodium hydroxide is added until a pH in the region of 5-6 is obtained. The solid formed is filtered off so as to give 1 g of 7-chloro-2,2-dimethyl-2,3-dihydro-1H-imidazo[1,2-a]pyrimidin-5-one, in the form of a brown solid, the characteristics of which are the following:
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:9][C:10]3[CH:16]=[CH:15][C:14]([C:17](O)=[O:18])=[CH:13][C:11]=3[CH:12]=2)=[CH:4][CH:3]=1>C1COCC1>[OH:18][CH2:17][C:14]1[CH:15]=[CH:16][C:10]2[O:9][C:8]([C:5]3[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][CH:4]=3)=[CH:12][C:11]=2[CH:13]=1
Reactant: O=C(O)c1ccc2oc(-c3ccc(O)cc3)cc2c1
Solvent: C1CCOC1
Product: OCc1ccc2oc(-c3ccc(O)cc3)cc2c1
Reaction time: 2 h
Yield: 35.1 %

Procedure:
Compound 143 (0.21 g, 0.83 mmol) in THF (10 ml) was treated with BH3 THF (4.0 ml of 1.0 M) and the reaction was heated to reflux. After 2 hr, the reaction was cooled and then poured into 2NHCl and extracted with EtOAc. The organic layer was dried, concentrated and the product was purified by cloumn chromatography (60% EtOAc/Hexane) to give 144 as a solid (0.07 g, 37%); Mp=248–250° C.; 1H NMR (DMSO-d6) δ 9.86 (br s, 1 H), 7.72 (d, 2 H, J=8.3 Hz), 7.52–7.49 (m, 2 H), 7.19 (dd, 1 H, J=8.3 Hz, 1.6 Hz), 7.15 (s, 1 H), 6.87 (d, 2 H, J=8.8 Hz), 5.19 (t, 1 H, J=5.2 Hz), 4.56 (d, 2 H, J=4.1 Hz); MS 239 (M−H)−.
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](O)=[C:14]([C:19]#[N:20])[CH:15]=[N:16]2)=[CH:11][C:10]=1[O:22][CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(Cl)(=O)C([Cl:27])=O>CCCCCC>[CH2:1]([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:27])=[C:14]([C:19]#[N:20])[CH:15]=[N:16]2)=[CH:11][C:10]=1[O:22][CH3:23])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)C(=O)Cl
Reactant: COc1cc2c(O)c(C#N)cnc2cc1OCc1ccccc1
Solvent: CCCCCC
Product: COc1cc2c(Cl)c(C#N)cnc2cc1OCc1ccccc1
Reaction time: 0.25 h

Procedure:
A total of 500 mg (1.63 mM) of 7-benzyloxy-4hydroxy-6-methoxy-quinoline-3-carbonitrile was taken up into 3 ml of oxalyl chloride (2M in CHCl3) and allowed to stand for 15 min followed by refluxing for 1 h. The solution was allowed to cool and then diluted with 300 mg of hexane to give a green solid. The solid was isolated and washed with excess hexane and dried under vacuum at 40° C. to yield 586 mg of 7-benzyloxy-4-chloro-6-methoxy-quinoline-3-carbonitrile as the hydrogen chloride salt. This compound was taken immediately on for the next step.
Reaction SMILES: C(OC1[CH:12]=[CH:11][C:8]([CH:9]=[CH2:10])=[CH:7][CH:6]=1)(=O)C.C(O[C:18]([O:20][C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])=O)(C)(C)C.[OH-].C[N+](C)(C)C>>[C:24]([O:23][C:21]([O:20][C:18]1[CH:10]=[CH:9][C:8]([CH:11]=[CH2:12])=[CH:7][CH:6]=1)=[O:22])([CH3:25])([CH3:26])[CH3:27]
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Reactant: C=Cc1ccc(OC(C)=O)cc1
Agent: C[N+](C)(C)C
Agent: [OH-]
Product: C=Cc1ccc(OC(=O)OC(C)(C)C)cc1
Temperature: 25 °C
Reaction time: 18 h
Yield: 8.9 %

Procedure:
To a single neck 250 ml round bottom were added 10.0 g (0.617 moles) of 4-acetoxystyrene, 13.46 g (0.617 moles) of di-t-butyldicarbonate and 52 ml (15% mole excess) of a 25 weight % solution of tetramethylammonium hydroxide and the resulting reaction mixture was stirred under nitrogen at room temperature for about 18 hours. The reaction mixture was extracted twice with ether (50 ml) and washed once with a 25 weight % solution of tetramethylammonium hydroxide (50 ml) and then twice with water (50 ml). The organic products were dried over magnesium sulfate and evaporated to dryness leaving a clear colorless oil (12.16 g, 90% yield).
Reaction SMILES: Br[C:2]1[N:6]=[CH:5][N:4]([C:7]2[CH:12]=[CH:11][C:10]([O:13][C:14]([F:17])([F:16])[F:15])=[CH:9][CH:8]=2)[N:3]=1.CC1(C)C(C)(C)OB([C:26]2[CH:31]=[CH:30][C:29]([CH2:32][CH2:33][CH2:34][N:35]3[C:43](=[O:44])[C:42]4[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:36]3=[O:45])=[CH:28][CH:27]=2)O1.C(=O)(O)[O-].[Na+].O1CCOCC1>C(OCC)(=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O>[F:15][C:14]([F:17])([F:16])[O:13][C:10]1[CH:11]=[CH:12][C:7]([N:4]2[CH:5]=[N:6][C:2]([C:26]3[CH:27]=[CH:28][C:29]([CH2:32][CH2:33][CH2:34][N:35]4[C:36](=[O:45])[C:37]5[C:42](=[CH:41][CH:40]=[CH:39][CH:38]=5)[C:43]4=[O:44])=[CH:30][CH:31]=3)=[N:3]2)=[CH:8][CH:9]=1
Reactant: FC(F)(F)Oc1ccc(-n2cnc(Br)n2)cc1
Reactant: CC1(C)OB(c2ccc(CCCN3C(=O)c4ccccc4C3=O)cc2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: O=C1c2ccccc2C(=O)N1CCCc1ccc(-c2ncn(-c3ccc(OC(F)(F)F)cc3)n2)cc1
Temperature: 140 °C

Procedure:
To 3-bromo-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole (C1) (0.50 g, 1.6 mmol), 2-(3-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propyl)isoindoline-1,3-dione (C58) (0.64 g, 1.6 mmol), sodium bicarbonate (0.27 g, 3.3 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.19 g, 0.16 mmol) in a 10-20 mL microwave vial equipped with a stir bar was added dioxane (12 mL) and water (4.1 mL). The reaction was capped and heated at 140° C. for 30 minutes in a Biotage Initiator® microwave reactor with external IR-sensor temperature monitoring from the side of the vessel. The mixture was diluted with ethyl acetate and washed with water. The aqueous layer was extracted with ethyl acetate. The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. Purification by flash column chromatography using 0-30% ethyl acetate/B, where B=1:1 dichloromethane/hexanes, as eluent provided a solid which was dried under house vacuum overnight. The title compound was obtained as a white solid (0.42 g, 53%): mp 145-148° C.; 1H NMR (400 MHz, CDCl3) δ 8.54 (d, J=0.8 Hz, 1H), 8.08 (d, J=8.1 Hz, 2H), 7.84 (ddd, J=5.5, 3.0, 0.8 Hz, 2H), 7.82-7.77 (m, 2H), 7.69 (ddd, J=5.5, 3.0, 0.8 Hz, 2H), 7.38 (dt, J=9.0, 1.0 Hz, 2H), 7.31 (d, J=8.0 Hz, 2H), 3.78 (t, J=7.2 Hz, 2H), 2.79-2.71 (m, 2H), 2.08 (p, J=7.5 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ −58.03; ESIMS m/z 493 ([M+H]+).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Cl:8])=[CH:4][N:3]=1.[CH3:9][C:10]([CH3:15])([CH3:14])[C:11](Cl)=[O:12]>C(Cl)Cl>[Cl:8][C:5]1[CH:6]=[CH:7][C:2]([NH:1][C:11](=[O:12])[C:10]([CH3:15])([CH3:14])[CH3:9])=[N:3][CH:4]=1
Reactant: Nc1ccc(Cl)cn1
Reactant: CC(C)(C)C(=O)Cl
Solvent: ClCCl
Product: CC(C)(C)C(=O)Nc1ccc(Cl)cn1
Temperature: 0 °C
Reaction time: 1 h
Yield: 102.8 %

Procedure:
TEA (6.78 mL, 48.6 mmol) was added to a suspension of 2-amino-5-chloropyridine (5.00 g, 38.9 mmol) in DCM (75 mL). The resulting solution was cooled to 0° C. and a solution of 2,2-dimethylpropanoyl chloride (5.74 mL, 46.7 mmol) in DCM (10.0 mL) was added dropwise over a 5 min period. The resulting mixture was allowed to stir at rt for 1 h. The reaction mixture was then transferred to a separatory funnel and washed with a saturated aqueous solution of NaHCO3. The organic solution was dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography to give N-(5-chloropyridin-2-yl)-2,2-dimethylpropanamide (8.0 g, 40 mmol, 99%). LCMS (FA): m/z=215.1 (M+H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:21])[CH2:13][CH2:12][N:11](C(OC(C)(C)C)=O)[CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1.FC(F)(F)C(O)=O>ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([OH:21])[CH2:13][CH2:12][NH:11][CH2:10]2)[CH:5]=[C:6]([F:8])[CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCC(O)(c2cc(F)cc(Cl)c2)C1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: OC1(c2cc(F)cc(Cl)c2)CCNC1
Reaction time: 4 h

Procedure:
Preparation according to Preparation 2: tert-Butyl 3-(3-Chloro-5-fluorophenyl)-3-hydroxypyrrolidin-1-carboxylate (1.6 g, 5.08 mmol), dichloromethane (3 mL) and trifluoroacetic acid (3 mL). Stirred for 4 h. Purification on a Biotage (solute SCX-3 SPE column (washed with methanol and eluted with methanol/triethylamine, 4:1) and by HPLC on Waters OBD C18, 5 μm (MeOH/33 mM NH3, 20:80 to 100:0). Yield: 1.1 g. MS m/z (rel. intensity, 70 eV) 215 (M+, bp), 129 (65), 109 (52), 157 (46), 95 (44).
Reaction SMILES: [C:1]([O:5][C:6](=[O:44])[NH:7][C@@H:8]([C@H:35]([CH3:43])[CH2:36][CH:37]([CH3:42])[CH2:38][CH2:39][CH:40]=C)[C:9]([N:11]1[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]1[C:17](=[O:34])[NH:18][C@:19]1([C:24](=[O:33])[NH:25][S:26]([C:29]2([CH3:32])[CH2:31][CH2:30]2)(=[O:28])=[O:27])[CH2:21][C@H:20]1[CH:22]=C)=[O:10])([CH3:4])([CH3:3])[CH3:2]>ClCCCl.CC1C=C(C)C(N2C(=[Ru](Cl)(Cl)=CC3C=CC=CC=3OC(C)C)N(C3C(C)=CC(C)=CC=3C)CC2)=C(C)C=1>[C:1]([O:5][C:6](=[O:44])[NH:7][C@@H:8]1[C:9](=[O:10])[N:11]2[CH2:15][C@H:14]([OH:16])[CH2:13][C@H:12]2[C:17](=[O:34])[NH:18][C@:19]2([C:24](=[O:33])[NH:25][S:26]([C:29]3([CH3:32])[CH2:30][CH2:31]3)(=[O:27])=[O:28])[CH2:21][C@H:20]2[CH:22]=[CH:40][CH2:39][CH2:38][CH:37]([CH3:42])[CH2:36][C@H:35]1[CH3:43])([CH3:4])([CH3:3])[CH3:2]
Reactant: C=CCCC(C)C[C@@H](C)[C@H](NC(=O)OC(C)(C)C)C(=O)N1C[C@H](O)C[C@H]1C(=O)N[C@]1(C(=O)NS(=O)(=O)C2(C)CC2)C[C@H]1C=C
Agent: Cc1cc(C)c(N2CCN(c3c(C)cc(C)cc3C)C2=[Ru](Cl)(Cl)=Cc2ccccc2OC(C)C)c(C)c1
Agent: CC1CC/C=C\[C@@H]2C[C@@]2(C(=O)NS(=O)(=O)C2(C)CC2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)OC(C)(C)C)[C@H](C)C1
Solvent: ClCCCl
Product: CC1CCC=C[C@@H]2C[C@@]2(C(=O)NS(=O)(=O)C2(C)CC2)NC(=O)[C@@H]2C[C@@H](O)CN2C(=O)[C@@H](NC(=O)OC(C)(C)C)[C@H](C)C1
Temperature: 80 °C

Procedure:
A solution of tert-butyl((2S,3R)-1-((2S,4R)-4-hydroxy-2-(((1R,2S)-1-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-2-vinylcyclopropyl)carbamoyl)pyrrolidin-1-yl)-3,5-dimethyl-1-oxonon-8-en-2-yl)carbamate (8.4 g, 13.15 mmol) in DCE (1500 ml) was degassed with nitrogen for 30 min. and then (1,3-Bis-(2,4,6-trimethylphenyl)-2-imidazolidinylidene)dichloro(o-isopropoxyphenylmethylene)ruthenium) (“Hoveyda-Grubbs Catalyst 2nd Generation”, 0.413 g, 0.657 mmol) was added. The reaction solution was heated to 80° C. for 2 h. The reaction solution was concentrated in vacuo the and resulting residue was purified by silica gel chromatography using a gradient of 20-60% Acetone in hexanes to give the mixture of diastereomers tert-butyl((2R,6S,7R,13aS,14aR,16aS,Z)-2-hydroxy-7,9-dimethyl-14a-(((1-methylcyclopropyl)sulfonyl)carbamoyl)-5,16-dioxo-1,2,3,5,6,7,8,9,10,11,13a,14,14a,15,16,16a-hexadecahydrocyclopropa[e]pyrrolo[1,2-a][1,4]diazacyclopentadecin-6-yl)carbamate as a brown solid (5.6 g, 70% yield). MS: MS m/z 611.3 (M++1).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[CH:4][C:5]([N+:12]([O-])=O)=[C:6](S(O)(=O)=O)[CH:7]=1.O[C:16]1[CH:21]=[CH:20][C:19]([N+:22]([O-])=O)=[CH:18][C:17]=1S(O)(=O)=O.ClC1C=CC([N+]([O-])=O)=C(S(O)(=O)=O)C=1.ClC1C=CC([N+]([O-])=O)=CC=1S(O)(=O)=O.[OH-].[Na+]>[C].[Pd]>[CH:6]1[C:5]([NH2:12])=[CH:4][CH:3]=[C:2]([O:1][C:16]2[CH:17]=[CH:18][C:19]([NH2:22])=[CH:20][CH:21]=2)[CH:7]=1
Reactant: O=[N+]([O-])c1ccc(O)cc1S(=O)(=O)O
Reactant: O=[N+]([O-])c1ccc(O)c(S(=O)(=O)O)c1
Agent: [Pd]
Agent: O=[N+]([O-])c1ccc(Cl)c(S(=O)(=O)O)c1
Agent: O=[N+]([O-])c1ccc(Cl)cc1S(=O)(=O)O
Product: Nc1ccc(Oc2ccc(N)cc2)cc1

Procedure:
A 5-hydroxy-2-nitrobenzenesulfonic acid derivative (e.g. sodium 5-hydroxy-2-nitrobenzenesulfonate) or a 2-hydroxy-5-nitrobenzenesulfonic acid derivative (e.g. sodium 2-hydroxy-5-nitrobenzenesulfonate) is reacted with a 5-chloro-2-nitrobenzenesulfonic acid derivative or a 2-chloro-5-nitrobenzenesulfonic acid derivative in the presence of an alkali (e.g. sodium hydroxide), followed by hydrogenation using palladium-carbon, to give the corresponding 4,4′-diaminodiphenyl ether derivative. This is diazotized using sodium nitrite under acidic conditions in the presence of hydrochloric acid, followed by reaction with sodium azide, to give the desired product.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:13])=[C:6]([C:8](=O)[CH:9]([F:11])[F:10])[CH:7]=1.[CH3:14][C:15]([S@@:18]([NH2:20])=[O:19])([CH3:17])[CH3:16]>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([F:13])=[C:6](/[C:8](=[N:20]\[S@:18]([C:15]([CH3:17])([CH3:16])[CH3:14])=[O:19])/[CH:9]([F:11])[F:10])[CH:7]=1
Reactant: CC(C)(C)[S@@](N)=O
Reactant: O=C(c1cc(Br)ccc1F)C(F)F
Product: CC(C)(C)[S@](=O)/N=C(\c1cc(Br)ccc1F)C(F)F
Yield: 78 %

Procedure:
Starting from 1-(5-bromo-2-fluorophenyl)-2,2-difluoroethanone and (S)-(−)-2-methyl-2-propanesulfinamide, the (S,E)-N-(1-(5-bromo-2-fluorophenyl)-2,2-difluoroethylidene)-2-methylpropane-2-sulfinamide (14.49 g, 78.0% yield) was obtained as a yellow oil. MS (ISP): m/z=355.9 [M+H]+ and 357.9 [M+2+H]+.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[C:6]([CH:8]([CH3:10])[CH3:9])[CH:5]=[CH:4][C:3]=1[CH:11]([CH3:13])[CH3:12].[Cl:14][S:15](O)(=[O:17])=[O:16]>C(Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[C:3]([CH:11]([CH3:13])[CH3:12])=[CH:4][C:5]([S:15]([Cl:14])(=[O:17])=[O:16])=[C:6]([CH:8]([CH3:9])[CH3:10])[CH:7]=1
Reactant: CC(C)c1ccc(C(C)C)c(Br)c1
Reactant: O=S(=O)(O)Cl
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)c1cc(S(=O)(=O)Cl)c(C(C)C)cc1Br

Procedure:
To a one-liter flask containing 80 parts of 2-bromo-1,4-diisopropylbenzene in 320 parts of carbon tetrachloride, there is added over 15 min. 154 parts of chlorosulfonic acid. After stirring thirty min. longer, the reaction mixture is poured onto 1000 parts of ice. The organic layer is separated and washed with 200 parts of water and then dried over magnesium sulfate. Removal of the solvent under reduced pressure gives 105 parts of 4-bromo-2,5-diisopropylbenzenesulfonyl chloride which can be recrystallized from n-hexane, m.p. 80°-83°.
Reaction SMILES: S(Cl)(Cl)=O.[Cl:5][C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[CH2:13][CH2:14][C:15]([OH:17])=O>C(Cl)Cl>[Cl:5][C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[C:8]2[C:7]=1[CH2:13][CH2:14][C:15]2=[O:17]
Reactant: O=C(O)CCc1ccc(Cl)cc1Cl
Solvent: O=S(Cl)Cl
Solvent: ClCCl
Product: O=C1CCc2c(Cl)cc(Cl)cc21
Yield: 74.6 %

Procedure:
Thionyl chloride (36.9 g) was added dropwise at 40° C. to a solution of 3-(2,4-di-chlorophenyl)propionic acid (43.8 g) in methylene chloride (200 ml). After reaction was complete, excess thionyl chloride and the solvent were removed by distillation. The oily residue was added dropwise at 40° C. to a suspension of aluminium chloride (53.3 g) in methylene chloride (200 ml). The reaction mixture was added to dilute hydrochloric acid after 18 hours at 40° C. The aqueous phase was separated off and extracted once with methylene chloride (250 ml). The combined organic phases were freed from the solvent. The residue was recrystallized from cyclohexane. 30 g of a colorless solid (m.p.: 115-116° C.) were obtained.
Reaction SMILES: [F:1][C:2]([F:11])([F:10])[C:3](=O)[CH2:4][C:5](=O)[CH2:6][CH3:7].O.[NH2:13][NH2:14]>C(O)(=O)C.O>[CH2:6]([C:5]1[NH:14][N:13]=[C:3]([C:2]([F:11])([F:10])[F:1])[CH:4]=1)[CH3:7]
Reactant: CCC(=O)CC(=O)C(F)(F)F
Reactant: NN
Solvent: O
Solvent: CC(=O)O
Product: CCc1cc(C(F)(F)F)n[nH]1
Yield: 59.2 %

Procedure:
A solution of 1,1,1-trifluoro-2,4-hexane-dione (2.4 g, 14.3 mmol), hydrazine hydrate (1.0 g, 19.0 mmol) and acetic acid (1 drop) in water (10 mL) was heated to reflux for 1 h. The reaction mixture was then cooled in an ice bath to form a white precipitate. The precipitate was then filtered, dissolved in chloroform and dried over MgSO4. The resulting solution was concentrated under reduced pressure to provide 1.39 g of the title compound. This compound was of sufficient purity to use in subsequent reactions.
Reaction SMILES: O[CH2:2][C:3]1[C:8]([C:9]([NH2:11])=O)=[CH:7][CH:6]=[CH:5][N:4]=1.P(Cl)(Cl)([Cl:14])=O.O.[OH-].[Na+]>C(#N)C.C1(C)C=CC=CC=1>[C:9]([C:8]1[C:3]([CH2:2][Cl:14])=[N:4][CH:5]=[CH:6][CH:7]=1)#[N:11]
Reactant: NC(=O)c1cccnc1CO
Reactant: O=P(Cl)(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: Cc1ccccc1
Solvent: CC#N
Product: N#Cc1cccnc1CCl
Temperature: 78 °C
Reaction time: 0.25 h

Procedure:
20.0 g (131.45 mmol) of 2-hydroxymethyl-3-pyridinecarboxamide are suspended in 110 ml of acetonitrile and heated to 78° C. Within 15 minutes, 60.65 g (395.52 mmol) of phosphorus oxychloride are metered in and the mixture is heated to 81° C. for 2 hours. After cooling at 22° C., the reaction mixture is stirred into 200 ml of water at 40° C. After 100 ml of toluene have been added, the mixture is neutralized with sodium hydroxide solution with cooling. After phase separation, the organic phase is washed with 100 ml of water. Removal of the organic phase and evaporation of the solvent under reduced pressure gives rise initially to an oily residue which crystallizes on standing.
Reaction SMILES: Cl.[CH3:2][O:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([NH2:10])=[NH:9])=[CH:6][CH:5]=1.[C:13](OCC)(=[O:18])[CH2:14][C:15]([CH3:17])=O.C(=O)([O-])[O-].[K+].[K+]>C(O)C>[OH:18][C:13]1[CH:14]=[C:15]([CH3:17])[N:10]=[C:8]([C:7]2[CH:11]=[CH:12][C:4]([O:3][CH3:2])=[CH:5][CH:6]=2)[N:9]=1
Reactant: COc1ccc(C(=N)N)cc1
Reactant: CCOC(=O)CC(C)=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCO
Product: COc1ccc(-c2nc(C)cc(O)n2)cc1
Reaction time: 7 h

Procedure:
To the mixture of 10 g of 4-methoxybenzamidine hydrochloride, 7.7 g of ethyl acetoacetate and 16.3 g of potassium carbonate were added 120 ml of ethanol, and the mixture was heat-refluxed with stirring for 7 hours. The reaction mixture was cooled and filtered to remove insoluble substances. The filtrate was evaporated. Water was added to the residue to dissolve and then the resulting solution was neutralized with acetic acid. The precipitated crystals were filtered off, washed with water and dried. Whereby 10.9 g of the desired substance was obtained as white crystals. Melting point is 202° to 203° C.
Reaction SMILES: [C:1]([O:6][CH2:7][CH3:8])(=[O:5])[CH:2]([CH3:4])[CH3:3].[Br:9][CH2:10][CH2:11][CH2:12][CH2:13]Br>>[Br:9][CH2:10][CH2:11][CH2:12][CH2:13][C:2]([CH3:4])([CH3:3])[C:1]([O:6][CH2:7][CH3:8])=[O:5]
Reactant: CCOC(=O)C(C)C
Reactant: BrCCCCBr
Product: CCOC(=O)C(C)(C)CCCCBr

Procedure:
Using ethyl isobutyrate and 1,4-dibromobutane, the same reaction as in Reference Example 16 was conducted to produce the title compound. b.p. 62°-64° C./0.4 mmHg
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[OH:9].Br[CH2:11][CH2:12][CH2:13][N:14]1[C:18](=[O:19])[C:17]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:16]2[C:15]1=[O:24].C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Cl:8])[C:3]=1[O:9][CH2:11][CH2:12][CH2:13][N:14]1[C:18](=[O:19])[C:17]2=[CH:20][CH:21]=[CH:22][CH:23]=[C:16]2[C:15]1=[O:24]
Reactant: O=C1c2ccccc2C(=O)N1CCCBr
Reactant: Oc1c(Cl)cccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1c2ccccc2C(=O)N1CCCOc1c(Cl)cccc1Cl
Temperature: 100 °C
Reaction time: 4 h
Yield: 99.2 %

Procedure:
A mixture of 2,6-dichlorophenol (2.0 g, 12 mmol), N-(3-bromopropyl)phthalimide (3.29 g, 12 mmol) and potassium carbonate (1.69 g, 12 mmol) in anhydrous N,N-dimethylformamide (40 ml) was stirred at 100° C. for 4 hours under an atmosphere of nitrogen. The mixture was then poured into 200 ml of distilled water to give a white precipitate, which was filtered and washed with distilled water. The solid was dried in a vacuum desiccator to yield 4.17 g of N-[3(2,6-dichlorophenoxy)propyl] phthalimide which was dissolved in absolute ethanol (75 ml) and hydrazine hydrate (3 ml, 73 mmol) was added and the mixture refluxed for one hour. After cooling to room temperature, the precipitate was filtered off and the filtrate was concentrated. The residue was chromatographed on silica gel column and eluted with dichloromethane/methanol/ammonium hydroxide (9:2:0.2) to yield 3.2 g of 3-(2,6-dichorophenoxy)propylamine.