Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([C@@H:12]3[CH2:15][C@H:14]([CH2:16]OS(C4C=CC(C)=CC=4)(=O)=O)[CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH:28]1[CH2:31][CH2:30][CH2:29]1>CN(C=O)C>[N:28]1([CH2:16][C@@H:14]2[CH2:13][C@H:12]([N:8]3[C:4]4[N:5]=[CH:6][N:7]=[C:2]([NH2:1])[C:3]=4[C:10]([I:11])=[CH:9]3)[CH2:15]2)[CH2:31][CH2:30][CH2:29]1
Reactant: C1CNC1
Reactant: Cc1ccc(S(=O)(=O)OC[C@H]2C[C@@H](n3cc(I)c4c(N)ncnc43)C2)cc1
Solvent: CN(C)C=O
Product: Nc1ncnc2c1c(I)cn2[C@H]1C[C@@H](CN2CCC2)C1

Procedure:
The DMF (3 mL) solution of cis-toluene-4-sulfonic acid 3-(4-amino-5-iodopyrrolo[2,3-d]pyrimidin-7-yl)-cyclobutylmethyl ester (see above for its preparation) (63 mg, 80% purity, 0.10 mmol) and azetidine (12 mg, 2 eq.) was stirred at 50° C. overnight in a sealed tube. The reaction mixture was used directly for further reaction. MS (ES+): 384.1 [MH+]. HPLC: tR=1.4 min (polar—5 min). For 1H NMR analysis, a small sample was taken out for HPLC purification. 1H NMR (DMSO-d6, 400 MHz): δ=1.99-2.06 (quintet, 2H, J=6.9 Hz), 2.08-2.22 (m, 3H), 2.49-2.53 (m, 2H), 2.54-2.56 (d, 2H, J=6.4 Hz), 3.15-3.19 (d, 4H, J=7.2 Hz), 5.01-5.10 (quintet, 2H, J=8.7 Hz), 6.69 (brs, 2H), 7.80 (s, 1H), 8.16 (s, 1H).
Reaction SMILES: [Br:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([N:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20](OC4C(F)=C(F)C(F)=C(F)C=4F)(=[O:22])=[O:21])=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:35])=[C:4]([O:36][CH3:37])[CH:3]=1.[O:38]1[CH:42]=[CH:41][C:40]([NH2:43])=[N:39]1.C1COCC1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+]>CCOC(C)=O>[Br:1][C:2]1[C:7]([C:8]#[N:9])=[CH:6][C:5]([N:10]2[C:19]3[C:14](=[CH:15][C:16]([S:20]([NH:43][C:40]4[CH:41]=[CH:42][O:38][N:39]=4)(=[O:21])=[O:22])=[CH:17][CH:18]=3)[CH:13]=[CH:12][C:11]2=[O:35])=[C:4]([O:36][CH3:37])[CH:3]=1
Reactant: COc1cc(Br)c(C#N)cc1-n1c(=O)ccc2cc(S(=O)(=O)Oc3c(F)c(F)c(F)c(F)c3F)ccc21
Reactant: Nc1ccon1
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: COc1cc(Br)c(C#N)cc1-n1c(=O)ccc2cc(S(=O)(=O)Nc3ccon3)ccc21
Reaction time: 0.25 h
Yield: 67.1 %

Procedure:
A RBF was charged with perfluorophenyl 1-(4-bromo-5-cyano-2-methoxyphenyl)-2-oxo-1,2-dihydroquinoline-6-sulfonate (330.64 mg, 0.550 mmol), isoxazol-3-amine (46.7 μl, 0.632 mmol) and THF (3666 μl) to give a clear solution. The flask was cooled in an ice-water bath for 10 min, then lithium bis(trimethylsilyl)amide (1M in THF) (1155 μl, 1.155 mmol) was added dropwise. After 15 min, the mixture was diluted with EtOAc and washed with 1N aq. HCl. The aq. layer was extracted with EtOAc (2×). The combined organic extracts were dried over sodium sulfate, filtered, and concentrated. The residue was purified by chromatography (45-g Redi-Sep column, 25-g silica gel loading column, 0-5% MeOH/DCM) to give 1-(4-bromo-5-cyano-2-methoxyphenyl)-N-(isoxazol-3-yl)-2-oxo-1,2-dihydroquinoline-6-sulfonamide (185 mg, 0.369 mmol, 67.1% yield) as a light-yellow solid. 1 H NMR (400 MHz, DMSO-d6) □=11.67 (br. s., 1 H), 8.73 (d, J=1.8 Hz, 1 H), 8.38 (d, J=2.2 Hz, 1 H), 8.27-8.21 (m, 1 H), 8.12-8.06 (m, 1 H), 7.90-7.78 (m, 2 H), 6.90 (d, J=9.0 Hz, 1 H), 6.85-6.76 (m, 1 H), 6.45 (d, J=1.8 Hz, 1 H), 3.81 (s, 3 H). m/z/(ESI) 501.0 (M+H)+.
Reaction SMILES: [S:1]([C:9]1[CH:15]=[CH:14][C:12]([CH3:13])=[CH:11][CH:10]=1)([O:4][CH:5]=[C:6]([F:8])[F:7])(=[O:3])=[O:2].[S:16]([O-:19])([OH:18])=[O:17].[Na+:20].C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1>O.CO>[F:8][C:6]([F:7])([S:16]([O-:19])(=[O:18])=[O:17])[CH2:5][O:4][S:1]([C:9]1[CH:15]=[CH:14][C:12]([CH3:13])=[CH:11][CH:10]=1)(=[O:3])=[O:2].[Na+:20]
Reactant: O=S([O-])O
Reactant: Cc1ccc(S(=O)(=O)OC=C(F)F)cc1
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Agent: [Na+]
Solvent: CO
Solvent: O
Product: Cc1ccc(S(=O)(=O)OCC(F)(F)S(=O)(=O)[O-])cc1
Temperature: 80 °C
Reaction time: 40 h
Yield: 16 %

Procedure:
9.3 g of 2,2-difluoroethenyl tosylate, which had been synthesized by a conventional technique, was dispersed in 17 g of water and 37 g of methanol, after which 4.7 g of sodium hydrogen sulfite and 0.5 g of benzoyl peroxide were added. The reaction mixture was stirred at 80° C. for 40 hours. The reaction solution was allowed to cool, after which methanol was distilled off in vacuum. Toluene was added, followed by separatory operation to separate a water layer. A saturated sodium chloride aqueous solution was added to the water layer whereupon white crystals settled out. The crystals were collected by filtration, washed with a small volume of saturated sodium chloride aqueous solution and then dried in vacuum, obtaining the target compound, sodium 1,1-difluoro-2-tosyloxyethanesulfonate. White crystals, 2.5 g (yield 16%).
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[C:10]2[C:5]([CH2:6][CH2:7][C:8](=[O:22])[N:9]2[CH2:12][CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])=[CH:4][CH:3]=1.[CH:23]1([NH:29][C:30]2[CH:38]=[C:37]([C:39]([F:42])([F:41])[F:40])[CH:36]=[CH:35][C:31]=2[C:32](O)=[O:33])[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]1.Cl.C(N=C=NCCCN(C)C)C.CN(C1C=CC=CN=1)C>C(N(CC)CC)C.C(Cl)Cl>[Si:15]([O:14][CH2:13][CH2:12][N:9]1[C:10]2[C:5](=[CH:4][CH:3]=[C:2]([NH:1][C:32](=[O:33])[C:31]3[CH:35]=[CH:36][C:37]([C:39]([F:41])([F:42])[F:40])=[CH:38][C:30]=3[NH:29][CH:23]3[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]3)[CH:11]=2)[CH2:6][CH2:7][C:8]1=[O:22])([C:18]([CH3:19])([CH3:21])[CH3:20])([CH3:16])[CH3:17]
Reactant: CC(C)(C)[Si](C)(C)OCCN1C(=O)CCc2ccc(N)cc21
Reactant: O=C(O)c1ccc(C(F)(F)F)cc1NC1CCCCC1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccccn1
Agent: Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC(C)(C)[Si](C)(C)OCCN1C(=O)CCc2ccc(NC(=O)c3ccc(C(F)(F)F)cc3NC3CCCCC3)cc21

Procedure:
A methylene chloride solution of 7-amino-1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-3,4-dihydroquinolin-2(1H)-one, 2-(cyclohexylamino)-4-(trifluoromethyl)benzoic acid, 1-ethyl-3-[3-(N,N-dimethylamino)propyl]carbodiimide hydrochloride, dimethylaminopyridine and triethylamine was allowed to undergo the reaction at room temperature. By post-treating the reaction liquid, N-[1-(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)-2-oxo-1,2,3,4-tetrahydroquinolin-7-yl]-2-(cyclohexylamino)-4-(trifluoromethyl)benzamide was obtained.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH2:19][C:20]([CH3:28])([CH3:27])[CH2:21][C:22]([O:24]CC)=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH2:11][NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1.FC(F)(F)C(O)=O>CO.[OH-].[Na+]>[F:1][C:2]1[CH:3]=[C:4]([CH2:19][C:20]([CH3:28])([CH3:27])[CH2:21][C:22]([OH:24])=[O:23])[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][CH2:10][CH2:11][NH:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][N:14]=1
Reactant: CCOC(=O)CC(C)(C)Cc1ccc(OCCCNc2ccccn2)c(F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Product: CC(C)(CC(=O)O)Cc1ccc(OCCCNc2ccccn2)c(F)c1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
The product of STEP 8 (370 mg, 0.95 mmol) was dissolved in 20 ml methanol and 20 ml 1N sodium hydroxide solution . The reaction was stirred at room temperature for 16 h, and acidified with trifluoroacetic acid (3 ml). Solvents were evaporated and residue was purified on HPLC using acetonitrile gradient 10-50% in 30 min to yield 300 mg. FAB-MS: (MH+)=361. H NMR(CDCl3) δ1.03 (s, 6H), 2.20 (s, 2H), 2.22 (p, 2H), 2.62 (s, 2IH), 3.58 (q, 2H), 4.14 (t, 2H), 6.72 (t, 1H), 6.86-6.98 (m, 4H), 7.70 (m, 2H); Anal. Calcd. for C20H25N2O3F plus 1.4 CF3COOH: C, 52.66; H, 5.12; N, 5.39. Found: C, 52.56; H, 5.23; N, 5.09.
Reaction SMILES: C([O:3][C:4](=[O:26])[C:5](=[O:25])[CH2:6][C:7](=[O:24])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:17][CH2:16][CH2:15]2)[CH:9]=1)C.[OH-].[Na+]>CO.O>[O:25]=[C:5]([CH2:6][C:7](=[O:24])[C:8]1[CH:13]=[CH:12][CH:11]=[C:10]([CH:14]2[C:23]3[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=3)[CH2:17][CH2:16][CH2:15]2)[CH:9]=1)[C:4]([OH:26])=[O:3]
Reactant: CCOC(=O)C(=O)CC(=O)c1cccc(C2CCCc3ccccc32)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: O=C(O)C(=O)CC(=O)c1cccc(C2CCCc3ccccc32)c1
Reaction time: 4 h

Procedure:
Isomer A: 2,4-dioxo-4-[3-(1,2,3,4-tetrahydronaphthalen-1-yl)-phenyl]butyric acid ethyl ester (isomer A from above) was dissolved in 2 mLs methanol, and to it was added 1 mL of a 1M solution of sodium hydroxide in water. After stirring for 4 hr, the reaction was poured into 5 mL sodium hydroxide and extracted three times with diethyl ether. The aqueous layer was then acidified via the addition of excess 10% citric acid and extracted three times with ethyl acetate. The ethyl acetate extracts were combined and washed with water, brine, dried over anhydrous sodium sulfate, filtered, and the solvent removed in vacuo. The residue was triturated in 3:1 hexane/diethyl ether, filtered and the solvent removed in vacuo to yield the title compound as a yellow solid. 1H NMR (CDCl3) δ1.72-1.91(3H,m), 2.20(1H,m), 2.80-3.00(2H,m), 4.22(1H, t, J=7.14Hz), 6.77(1H, d, J=7.69 Hz), 7.03(1H, t, J=7.42Hz), 7.11-7.19(3H,m), 7.31(1H, d, J=7.69Hz), 7.41(1H, t, J=7.69Hz), 7.80(1H,s), 7.84(1H, d, J=7.88Hz).
Reaction SMILES: [CH2:1]([O:7][C:8]1[CH:9]=[C:10]([C:20]([OH:22])=O)[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:12][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].S(Cl)([Cl:25])=O>>[CH2:1]([O:7][C:8]1[CH:9]=[C:10]([C:20]([Cl:25])=[O:22])[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:12][CH:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CCCCCCOc1ccc(-c2ccccc2)c(C(=O)O)c1
Reactant: O=S(Cl)Cl
Product: CCCCCCOc1ccc(-c2ccccc2)c(C(=O)Cl)c1

Procedure:
4-n-Hexyloxybiphenyl carboxylic acid (3.0 g) and an excessive amount of thionyl chloride were heated under refluxing for 6 hours. Unaltered thionyl chloride was distilled off to obtain 4-n-hexyloxybiphenyl carboxylic acid chloride.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[O:9][C:8]([CH:11](Br)Br)=[CH:7][C:6]=2[C:5]([C:14]2[C:15](=[O:25])[N:16]([CH3:24])[C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=2)=[C:4]([F:26])[CH:3]=1.S(=O)(=O)(O)[OH:28]>O>[Cl:1][C:2]1[C:10]2[O:9][C:8]([CH:11]=[O:28])=[CH:7][C:6]=2[C:5]([C:14]2[C:15](=[O:25])[N:16]([CH3:24])[C:17]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:19]=2)=[C:4]([F:26])[CH:3]=1
Reactant: O=S(=O)(O)O
Reactant: Cn1c(C(F)(F)F)ccc(-c2c(F)cc(Cl)c3oc(C(Br)Br)cc23)c1=O
Solvent: O
Product: Cn1c(C(F)(F)F)ccc(-c2c(F)cc(Cl)c3oc(C=O)cc23)c1=O
Temperature: 50 °C
Reaction time: 1 h
Yield: 96 %

Procedure:
0.29 g (0.56 mmol) of 3-(7-chloro-2-dibromomethyl-5-fluorobenzofuran-4-yl)-1-methyl-6-trifluoromethyl-2-(1H)-pyridone was added to 15 ml of sulfuric acid, followed by stirring at 50° C. for 1 hour. Then, the mixture was poured into water and extracted with diethyl ether. After washing with water, the organic layer was dried over anhydrous magnesium sulfate. Ethyl acetate was distilled off under reduced pressure. Then, the obtained crude crystals were washed with n-hexane to obtain 0.20 g (yield: 96%) of the desired product.
Reaction SMILES: FC(F)(F)C(O)=O.[CH3:8][C@@H:9]([O:13][C:14]1[NH:15][C:16]([NH2:25])=[C:17]2[C:21]([N:22]=1)=[N:20][C:19]([O:23][CH3:24])=[N:18]2)[CH2:10][CH2:11][CH3:12].Br[CH2:27][CH2:28][CH2:29][CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][O:33][CH2:32]1>>[CH3:8][C@@H:9]([O:13][C:14]1[N:22]=[C:21]2[C:17]([N:18]=[C:19]([O:23][CH3:24])[N:20]2[CH2:27][CH2:28][CH2:29][CH2:30][CH:31]2[CH2:36][CH2:35][CH2:34][O:33][CH2:32]2)=[C:16]([NH2:25])[N:15]=1)[CH2:10][CH2:11][CH3:12]
Reactant: CCC[C@@H](C)Oc1nc2nc(OC)nc-2c(N)[nH]1
Reactant: BrCCCCC1CCCOC1
Solvent: O=C(O)C(F)(F)F
Product: CCC[C@@H](C)Oc1nc(N)c2nc(OC)n(CCCCC3CCCOC3)c2n1

Procedure:
Prepared similarly to Intermediate 213 from 2-{[(1R)-1-methylbutyl]oxy}-8-(methyloxy)-1H-purin-6-amine trifluoroacetate and 3-(4-bromobutyl)tetrahydro-2H-pyran.
Reaction SMILES: [NH2:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([F:14])([F:13])[F:12])[CH:9]=2)[NH:4][N:3]=1.[CH:15](OC)=[O:16]>>[CH:15]([NH:1][C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([C:11]([F:12])([F:14])[F:13])[CH:9]=2)[NH:4][N:3]=1)=[O:16]
Reactant: COC=O
Reactant: Nc1n[nH]c2ccc(C(F)(F)F)cc12
Product: O=CNc1n[nH]c2ccc(C(F)(F)F)cc12

Procedure:
A mixture of 5.0 g. of 3-amino-5-trifluoromethylindazole, prepared as in Example 1, and 25 ml. of methyl formate is refluxed for eight hours, then concentrated in vacuo to leave crude 3-formylamino-5-trifluoromethylindazole.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([N:9]=[C:10]=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[NH2:13][CH2:14][C:15]1[CH:23]=[CH:22][CH:21]=[C:20]2[C:16]=1[CH2:17][N:18]([CH:25]1[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]1=[O:32])[C:19]2=[O:24].C(N(CC)CC)C>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]([NH:13][CH2:14][C:15]2[CH:23]=[CH:22][CH:21]=[C:20]3[C:16]=2[CH2:17][N:18]([CH:25]2[CH2:30][CH2:29][C:28](=[O:31])[NH:27][C:26]2=[O:32])[C:19]3=[O:24])=[O:11])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: O=C=Nc1ccc(Cl)c(Cl)c1
Reactant: NCc1cccc2c1CN(C1CCC(=O)NC1=O)C2=O
Agent: Cl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: O=C1CCC(N2Cc3c(CNC(=O)Nc4ccc(Cl)c(Cl)c4)cccc3C2=O)C(=O)N1
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.9 %

Procedure:
3,4-Dichlorophenyl isocyanate (0.5 g, 2.7 mmol) was added to a stirred suspension of 3-(4-aminomethyl-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione hydrochloride (0.7 g, 2.1 mmol) and triethylamine (0.3 g, 2.9 mmol) in THF (30 mL). The mixture was stirred at room temperature overnight. The mixture was concentrated, and the residue was stirred with 1N HCl (30 mL). The mixture was filtered, and the solid was slurried with hot methanol (20 mL) to give 1-(3,4-dichloro-phenyl)-3-[2-(2,6-dioxo-piperidin-3-yl)-1-oxo-2,3-dihydro-1H-isoindol-4-ylmethyl]-urea (0.6 g, 67%) as a white solid: mp 253-255° C.; 1H NMR (DMSO-d6) δ 2.00-2.05 (m, 1H), 2.37-2.65 (m, 2H), 2.86-3.00 (m, 1H), 4.36-4.58 (m, 4H, 2CH2), 5.11-5.18 (dd, J=4.9 and 13.1 Hz, 1H, CH), 6.89 (t, J=5.6 Hz, 1H, NH), 7.24-7.84 (m, 6H, Ar), 8.96 (s, 1H, NH), 11.01 (s, 1H, NH); 13C NMR (DMSO-d6) δ 22.56, 31.17, 39.69, 46.19, 51.58, 117.86, 118.83, 121.58, 122.37, 128.29, 130.38, 130.86, 131.64, 135.27, 139.91, 140.56, 154.87, 168.05, 170.98, 172.81; Anal. calcd. for C21H18N4O4Cl2: C, 54.68; H, 3.93; N, 12.15; Cl, 15.37. Found: C, 54.52; H, 3.78; N, 11.89; Cl, 15.28.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:30][C:12]2=[CH:13][C:14]3[C:15](=[O:29])[N:16]([CH:22]4[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]4)[C:17](=[O:21])[C:18]=3[C:19]([CH3:20])=[C:11]2[N:10]=1.[F:31][C:32]1[CH:33]=[CH:34][C:35]([CH3:42])=[C:36]([CH2:38][CH:39]([NH2:41])[CH3:40])[CH:37]=1.CCN(C(C)C)C(C)C>C(O)CCC>[F:31][C:32]1[CH:33]=[CH:34][C:35]([CH3:42])=[C:36]([CH2:38][CH:39]([NH:41][C:2]2[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=2[C:9]2[NH:30][C:12]3=[CH:13][C:14]4[C:15](=[O:29])[N:16]([CH:22]5[CH2:27][CH2:26][N:25]([CH3:28])[CH2:24][CH2:23]5)[C:17](=[O:21])[C:18]=4[C:19]([CH3:20])=[C:11]3[N:10]=2)[CH3:40])[CH:37]=1
Reactant: Cc1c2c(cc3[nH]c(-c4c(Cl)cc[nH]c4=O)nc13)C(=O)N(C1CCN(C)CC1)C2=O
Reactant: Cc1ccc(F)cc1CC(C)N
Solvent: CCCCO
Solvent: CCN(C(C)C)C(C)C
Product: Cc1ccc(F)cc1CC(C)Nc1cc[nH]c(=O)c1-c1nc2c(C)c3c(cc2[nH]1)C(=O)N(C1CCN(C)CC1)C3=O
Yield: 100.1 %

Procedure:
A mixture of 2-(4-chloro-2-oxo-1,2-dihydropyridin-3-yl)-4-methyl-6-(1-methylpiperidin-4-yl)imidazo[4,5-f]isoindole-5,7(1H,6H)-dione (1.00 g, 2.35 mmol), 1-(5-fluoro-2-methylphenyl)propan-2-amine (0.47 g, 2.82 mmol), Hunig's base (1.52 g, 0.011 mol), and 20 mL of anhydrous 1-butanol was heated at reflux for 14-15 h under an argon atmosphere. Product was purified by a silica gel column using methylene chloride and methanol (9:1 v/v) as eluent to afford 1.31 g (99%) of the designed compound as yellowish solid. 1H NMR (300 MHz, DMSO-d6) δ 13.37 (s, 1H, NH), 11.25 (d, J=6.3 Hz, 1H, NH), 11.02 (d, J=8.1 Hz, 1H, NH), 7.98 (s, 1H, ArH), 7.32 (t, J=7.2 Hz, 1H, ArH), 7.16-7.07 (m, 2H, ArH), 6.92-6.86 (m, 1H, ArH), 6.17 (d, J=7.5 Hz, 1H, ArH), 4.34-4.19 (m, 2H, 2×CH), 3.51-3.47 (m, 2H, CH2), 3.18-3.11 (m, 2H, CH2), 2.97 (d, J=6.3 Hz, 2H, CH2), 2.83 (s, 3H, CH3), 2.76 (s, 31-1, CH3), 2.69-2.61 (m, 2H, CH2), 2.27 (s, 3H, CH3), 1.95-1.91 (m, 2H, CH2), 1.34 (d, J=6.3 Hz, 3H, CH3); Mass (ESI, positive) m/z 557.2 [M+H]+.
Reaction SMILES: C(Cl)(=O)C(Cl)=O.[C:7]1([CH2:17][C:18]([OH:20])=O)[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9][CH:8]=1.[Cl-].[Al+3].[Cl-].[Cl-]>ClCCl.CN(C)C=O>[C:18]1(=[O:20])[C:15]2=[C:16]3[C:11](=[CH:12][CH:13]=[CH:14]2)[CH:10]=[CH:9][CH:8]=[C:7]3[CH2:17]1
Reactant: O=C(O)Cc1cccc2ccccc12
Agent: O=C(Cl)C(=O)Cl
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCl
Solvent: CN(C)C=O
Product: O=C1Cc2cccc3cccc1c23
Temperature: 0 °C
Reaction time: 1 h

Procedure:
In a 1 litre three-necked flask, oxalyl chloride (2.87 ml, 3.22.10−2 mol, 1 eq.) is added dropwise, under argon, to a solution of (naphth-1-yl)acetic acid (6 g, 3.22.10−2 mol) in anhydrous dichloromethane (270 ml) at 0° C. A few drops of anhydrous dimethylformamide are then added. After 1 hour at 0° C., slight evolution of gas is still observed and the three-necked flask is left at ambient temperature for 40 minutes. After return to 0° C., aluminium chloride (11.2 g, 8.38.10−2 mol, 2.6 eq.) is added gradually with a spatula. The solution is stirred for twenty minutes and becomes green-black in colour. The mixture is poured into an ice/1N HCl mixture. After separation of the phases and washings of the acidic aqueous phase with dichloromethane, the combined organic phases are washed with water, then treated with a saturated NaHCO3 solution and finally washed with a saturated NaCl solution. After drying over MgSO4 and evaporation under reduced pressure, the title product is obtained in the form of a yellow solid.
Reaction SMILES: [CH3:1][N:2]([CH3:11])[S:3]([N:6]1[CH:10]=[CH:9][CH:8]=[N:7]1)(=[O:5])=[O:4].[Cl:12]C(Cl)(Cl)C(Cl)(Cl)Cl.C([Li])CCC>>[Cl:12][C:8]1[CH:9]=[CH:10][N:6]([S:3]([N:2]([CH3:11])[CH3:1])(=[O:4])=[O:5])[N:7]=1
Reactant: ClC(Cl)(Cl)C(Cl)(Cl)Cl
Reactant: CN(C)S(=O)(=O)n1cccn1
Agent: [Li]CCCC
Product: CN(C)S(=O)(=O)n1ccc(Cl)n1

Procedure:
US 20130288893(A1) describes, inter alia, certain (3-halo-1-(pyridin-3-yl)-1H-pyrazol-4-yl)amides and carbamates and their use as pesticides. The route to prepare such compounds involved the preparation of 3-(3-chloro-1H-pyrazol-1-yl)pyridine (5b) by the direct coupling of 3-bromopyridine with 3-chloropyrazole. The 3-chloropyrazole was prepared by a) treating 1H-pyrazole with 2-dimethylsulfamoyl chloride and sodium hydride to provide N,N-dimethyl-1H-pyrazole-1-sulfonamide, b) treating the N,N-dimethyl-1H-pyrazole-1-sulfonamide with perchloroethane and n-butyl lithium to provide 3-chloro-N,N-dimethyl-1H-pyrazole-1-sulfonamide, and c) removing the N,N-dimethylsulfonamide from 3-chloro-N,N-dimethyl-1H-pyrazole-1-sulfonamide with trifluoroacetic acid to give the 3-chloropyrazole.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([OH:17])[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2].[Cl:19][C:20]1[N:24]=[C:23](Cl)[S:22][N:21]=1.C(=O)([O-])[O-].[Cs+].[Cs+].Cl>CN(C=O)C.O>[CH2:1]([O:3][C:4](=[O:18])[CH2:5][CH:6]1[O:10][B:9]([OH:11])[C:8]2[CH:12]=[C:13]([O:17][C:23]3[S:22][N:21]=[C:20]([Cl:19])[N:24]=3)[CH:14]=[C:15]([CH3:16])[C:7]1=2)[CH3:2]
Reactant: Clc1nsc(Cl)n1
Reactant: CCOC(=O)CC1OB(O)c2cc(O)cc(C)c21
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CN(C)C=O
Solvent: O
Product: CCOC(=O)CC1OB(O)c2cc(Oc3nc(Cl)ns3)cc(C)c21
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.8 %

Procedure:
To a solution of (1,6-dihydroxy-4-methyl-1,3-dihydro-benzo[c][1,2]oxaborol-3-yl)-acetic acid ethyl ester (1.0 g, 4.0 mmol) and 3,5-dichloro-1,2,4 thiadiazole (0.45 mL, 4.8 mmol) in DMF (24 mL) was added cesium carbonate (2.61 g, 8 mmol). The mixture was stirred at room temperature overnight. The reaction was diluted with H2O, acidified to pH 3 with aqueous HCl (1N). The mixture was extracted with ethyl acetate. The organic phase was separated, dried (Na2SO4), and concentrated. The residue was purified by column chromatography (silica, Ethyl acetate) affording the title compound (1.25 g, 85%) as a white solid: 1H NMR (CDCl3) δ7.48 (d, 1H), 7.19 (d, 1H), 5.68 (dd, 1H), 5.18 (s, 1H), 4.18 (q, 2H), 3.10 (dd, 1H), 2.45 (dd, 1H), 2.39 (s, 3H), 1.25 (t, 3H). MS found: (M+H)+=369.
Reaction SMILES: [O:1](C(OC(C)(C)C)=O)[C:2]([O:4][C:5]([CH3:8])([CH3:7])[CH3:6])=O.[F:16][C:17]([F:33])([F:32])[C:18]([C:24]1[CH:29]=[CH:28][C:27]([CH:30]=[CH2:31])=[CH:26][CH:25]=1)([OH:23])[C:19]([F:22])([F:21])[F:20].C([O-])([O-])=O.[K+].[K+]>C1COCC1>[C:2](=[O:1])([O:23][C:18]([C:24]1[CH:29]=[CH:28][C:27]([CH:30]=[CH2:31])=[CH:26][CH:25]=1)([C:19]([F:21])([F:20])[F:22])[C:17]([F:32])([F:33])[F:16])[O:4][C:5]([CH3:8])([CH3:7])[CH3:6]
Reactant: C=Cc1ccc(C(O)(C(F)(F)F)C(F)(F)F)cc1
Reactant: CC(C)(C)OC(=O)OC(=O)OC(C)(C)C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: C=Cc1ccc(C(OC(=O)OC(C)(C)C)(C(F)(F)F)C(F)(F)F)cc1
Temperature: 25 °C
Reaction time: 96 h

Procedure:
The title compound was prepared by a modification of the procedure of Przybilla, described in German Patent No. DE42072261A1 (Sep. 9, 1993), herein incorporated by reference. 9.35 mL of (t-BOC)2O (40.70 mmol) in THF (10 mL) was added to a mixture of 1,1,1,3,3,3-Hexafluoro-2-(4-vinylphenyl)-2-propanol (10.00 g, 37.01 mmol) and K2CO3 (10.00 g, 72.35 mmol) in THF (90 mL) was added. The reaction mixture was allowed to stir at room temperature for 4 days, concentrated, then partitioned between hexane/H2O. The aqueous solution was extracted with hexane, and the combined extracts were washed with brine, dried (Na2SO4), and concentrated to provide 15.17 g of a pale yellow oil. This material was purified by column chromatography on silica gel using 50:1 hexane/ethyl acetate to provide 5.16 g (38%) of a white solid, plus 4.68 g of a 90:10 mixture of protected/unprotected material; 1H NMR (CDCl3) δ 7.49 (d, 2ArH), 7.42 (d, 2ArH), 6.74 (dd, CH═), 5.83 (dd, ═CHH), 5.36 (dd, ═CHH), 1.49 (s, t-Bu).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([O:14][CH3:15])[C:5]2[O:9][C:8]([CH2:11][OH:12])([CH3:10])[CH2:7][C:6]=2[CH:13]=1.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19]([S:22](Cl)(=[O:24])=[O:23])=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C>CN(C)C1C=CN=CC=1>[CH3:26][C:16]1[CH:21]=[CH:20][C:19]([S:22]([O:12][CH2:11][C:8]2([CH3:10])[CH2:7][C:6]3[CH:13]=[C:2]([Cl:1])[CH:3]=[C:4]([O:14][CH3:15])[C:5]=3[O:9]2)(=[O:24])=[O:23])=[CH:18][CH:17]=1
Reactant: COc1cc(Cl)cc2c1OC(C)(CO)C2
Reactant: Cc1ccc(S(=O)(=O)Cl)cc1
Agent: CN(C)c1ccncc1
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(Cl)cc2c1OC(C)(COS(=O)(=O)c1ccc(C)cc1)C2
Yield: 76.7 %

Procedure:
Treatment of 4-chloro-2-methoxyphenol (15.00 g, 0.10 mol) with sodium hydride (4.4 g, 0.11 mol, 60 wt. %) and 3-chloro-2-methylpropene (12.00 g, 0.12 mol) generally according to the procedure described for Intermediate 13 provided 19.3 g (91%) of 4-chloro-2-methoxy-1-[(2-methylprop-2-enyl)oxy]benzene as a colorless oil. Treatment of the allyl ether in refluxing mesitylene generally according to the procedure described for Intermediate 8 afforded 15.5 g (78%) of 4-chloro-2-methoxy-6-(2-methylprop-2-enyl)phenol as a pale yellow oil. Treatment of 4-chloro-2-methoxy-6-(2-methylprop-2-enyl)phenol (10.00 g, 0.047 mol) with 3-chloroperoxybenzoic acid (20.00 g, 0.089 mol, 77%) followed by potassium carbonate (20.00 g, 0.145 mol) generally according to the Procedure described for Intermediate 9 provided 8.00 g (74%) of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methanol as a light yellow oil. Treatment of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methanol (10.8 g, 0.047 mol) with p-toluenesulfonyl chloride (13.5 g, 0.071 mol), diisopropylethylamine (12.15 g, 0.094 mol), and 4-(dimethylamino)pyridine (0.35 g, 2.83 mmol) generally according to the procedure described for Intermediate 45 gave 13.8 g (76%) of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-1-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid. mp 113-115° C.; Anal. calcd. for C18H19ClO5S: C, 56.47; H, 5.00. Found: C, 55.82; H, 4.94.