Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C[N:2](C)/[CH:3]=[CH:4]/[C:5]([C:7]1[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=2)[N:8]=1)=O.[F:26][C:27]1[CH:28]=[C:29]([NH:34]N)[CH:30]=[CH:31][C:32]=1[CH3:33]>>[F:26][C:27]1[CH:28]=[C:29]([N:34]2[C:5]([C:7]3[C:12](=[O:13])[CH:11]=[CH:10][N:9]([C:14]4[CH:19]=[CH:18][CH:17]=[C:16]([O:20][C:21]([F:24])([F:23])[F:22])[CH:15]=4)[N:8]=3)=[CH:4][CH:3]=[N:2]2)[CH:30]=[CH:31][C:32]=1[CH3:33]
Reactant: CN(C)/C=C/C(=O)c1nn(-c2cccc(OC(F)(F)F)c2)ccc1=O
Reactant: Cc1ccc(NN)cc1F
Product: Cc1ccc(-n2nccc2-c2nn(-c3cccc(OC(F)(F)F)c3)ccc2=O)cc1F

Procedure:
Reaction of 3-((E)-3-dimethylamino-acryloyl)-1-(3-trifluoromethoxy-phenyl)-1H-pyridazin-4-one (A-6) and (3-fluoro-4-methyl-phenyl)-hydrazine according to example 43 gave the desired product. MS: M=431.0 (M+H)+
Reaction SMILES: [CH2:1]([O:3][C:4]([CH2:6][CH2:7][Sn:8](Cl)(Cl)[CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:5])[CH3:2].[S-2:18].[Na+].[Na+]>C1(C)C=CC=CC=1>[CH2:1]([O:3][C:4]([CH2:6][CH2:7][Sn:8](=[S:18])[CH2:9][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[O:5])[CH3:2]
Reactant: [S-2]
Reactant: CCOC(=O)CC[Sn](Cl)(Cl)CCC(=O)OCC
Agent: [Na+]
Solvent: Cc1ccccc1
Product: CCOC(=O)CC[Sn](=S)CCC(=O)OCC

Procedure:
To a solution of 78.4g (0.2 mole) bis(ethoxycarbonylethylene)tin dichloride in 160 ml toluene was added 15.6g (0.2 mole) sodium sulfide as a 40% aqueous solution, while warming the mixture to maintain 85°-90° C. After the completion of the reaction, the layers were separated and the toluene solution of the product vacuum stripped to give the product as a viscous liquid, with refractive index 1.573 at 25° C and infra-red absorption peaks at 1700, 1660, and 1190. The product analyzed 33.9% tin, (C2H5OCOCH2CH2)2SnS requires 33.7% Sn.
Reaction SMILES: [CH2:1]([O:19][CH2:20][C:21]([CH2:65][O:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])([CH2:45][O:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64])[CH2:22][O:23][C:24]1[CH:36]=[CH:35][C:34]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=3)(O)[C:26]=2[CH:25]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18].C([Br:88])(=O)C>C(Cl)(Cl)Cl>[CH2:1]([O:19][CH2:20][C:21]([CH2:65][O:66][CH2:67][CH2:68][CH2:69][CH2:70][CH2:71][CH2:72][CH2:73][CH2:74][CH2:75][CH2:76][CH2:77][CH2:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH3:84])([CH2:45][O:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH2:53][CH2:54][CH2:55][CH2:56][CH2:57][CH2:58][CH2:59][CH2:60][CH2:61][CH2:62][CH2:63][CH3:64])[CH2:22][O:23][C:24]1[CH:36]=[CH:35][C:34]2[C:33]3[C:28](=[CH:29][CH:30]=[CH:31][CH:32]=3)[C:27]([C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=3)([Br:88])[C:26]=2[CH:25]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: CC(=O)Br
Reactant: CCCCCCCCCCCCCCCCCCOCC(COCCCCCCCCCCCCCCCCCC)(COCCCCCCCCCCCCCCCCCC)COc1ccc2c(c1)C(O)(c1ccc(Cl)cc1)c1ccccc1-2
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCCCCOCC(COCCCCCCCCCCCCCCCCCC)(COCCCCCCCCCCCCCCCCCC)COc1ccc2c(c1)C(Br)(c1ccc(Cl)cc1)c1ccccc1-2
Reaction time: 2 h
Yield: 78571432 %

Procedure:
2-(3-Octadecyloxy-2,2-bis-octadecyloxymethyl-propoxy)-9-(4-chlorophenyl)-9-fluorenol (66 mg, 56 μmol) was dissolved in chloroform (1 ml), acetyl bromide (41 μl, 0.55 mmol) was added dropwise thereto and the mixture was stirred for 2 hours. After completion of the reaction, the solvent was evaporated, and the residue was crystallized from acetonitrile (1 ml) to give 2-(3-octadecyloxy-2,2-bis-octadecyloxymethyl-propoxy)-9-(4-chlorophenyl)-9-bromofluorene (55 mg, 44 mol, 79%).
Reaction SMILES: [NH:1]([C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][CH:11]=1)[C:6]([OH:8])=[O:7])N.[CH:12]([C:15]([CH3:17])=O)([CH3:14])[CH3:13]>C(O)C.S(=O)(=O)(O)O>[CH3:17][C:15]1[C:12]([CH3:14])([CH3:13])[C:4]2[C:3](=[CH:11][CH:10]=[CH:9][C:5]=2[C:6]([OH:8])=[O:7])[N:1]=1
Reactant: NNc1cccc(C(=O)O)c1
Reactant: CC(=O)C(C)C
Agent: O=S(=O)(O)O
Solvent: CCO
Product: CC1=Nc2cccc(C(=O)O)c2C1(C)C
Temperature: 25 °C
Yield: 81.4 %

Procedure:
A solution of 3-hydrazinobenzoic acid (30.0 g, 197 mmol), isopropylmethylketone (31.7 mL, 296 mmol) in ethanol (500 mL) and sulfuric acid (5 mL) was heated under reflux in an oil bath for 20 h. After cooling to ambient temperature the solvent was evaporated off under reduced pressure to a small volume of ˜200 mL. Collected the solid with a filter funnel, washed with iPrOH (3×30 mL) and ethyl ether (3×30 mL) and dried. Further drying of the solid in an oven at 45° C. under high vacuum for 18 h provided 32.59 g (81.3%) of the product.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[NH:7][C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][CH2:21]O)[CH:11]=3)=[CH:9][C:2]=12.C(Br)(Br)(Br)[Br:24].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>ClCCl>[N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[NH:7][C:8]([C:10]3[C:18]4[C:13](=[CH:14][CH:15]=[CH:16][CH:17]=4)[N:12]([CH2:19][CH2:20][CH2:21][Br:24])[CH:11]=3)=[CH:9][C:2]=12
Reactant: BrC(Br)(Br)Br
Reactant: OCCCn1cc(-c2cc3nccnc3[nH]2)c2ccccc21
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: BrCCCn1cc(-c2cc3nccnc3[nH]2)c2ccccc21
Temperature: 25 °C
Reaction time: 3 h

Procedure:
To a solution of 3-[3-(5H-pyrrolo[2,3-b]pyrazin-6-yl)-indol-1-yl]-propan-1-ol [1 g, Example 2(a)] and carbon tetrabromide (1.59 g) in dichloromethane (40 mL) at ambient temperature was added a solution of triphenylphosphine (1.1 g) in dichloromethane (10 mL) over 2 minutes. The reaction mixture was stirred at ambient temperature for 3 hour, then stood for 18 hours and then evaporated to give the title compound which was used without further purification.
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[C:7]([C@H:23]2[CH2:27][CH2:26][C@H:25]([C:28]3[CH:33]=[C:32]([O:34][CH3:35])[C:31]([O:36][CH3:37])=[C:30]([O:38][CH3:39])[CH:29]=3)[O:24]2)[CH:8]=[C:9]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:10]=1[O:11][CH2:12][CH2:13][CH3:14])(=[O:4])=[O:3].C([Li])CCC.Br[CH:46]([OH:48])[CH3:47]>C1COCC1>[OH:48][CH2:46][CH2:47][CH2:1][S:2]([C:5]1[CH:6]=[C:7]([C@H:23]2[CH2:27][CH2:26][C@H:25]([C:28]3[CH:33]=[C:32]([O:34][CH3:35])[C:31]([O:36][CH3:37])=[C:30]([O:38][CH3:39])[CH:29]=3)[O:24]2)[CH:8]=[C:9]([O:15][CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[C:10]=1[O:11][CH2:12][CH2:13][CH3:14])(=[O:4])=[O:3]
Reactant: CCCOc1c(OCc2ccccc2)cc([C@H]2CC[C@H](c3cc(OC)c(OC)c(OC)c3)O2)cc1S(C)(=O)=O
Reactant: CC(O)Br
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: CCCOc1c(OCc2ccccc2)cc([C@H]2CC[C@H](c3cc(OC)c(OC)c(OC)c3)O2)cc1S(=O)(=O)CCCO
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
834 mg of trans-2-[3-methylsulfonyl-4-n-propoxy-5-benzyloxyphenyl]-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran dissolved in 8 ml of dry THF was cooled to -78° C. and to it was added 2 ml of n-butyllithium (1.6N solution in THF) in a nitrogen atmosphere. After 15 min. 140 mg of bromoethanol dissolved in 2 ml of THF was added to the reaction mixture. The yellow solution was warmed to room temperature and was quenched with a saturated NH4Cl solution. The title compound was obtained after workup and chromatography on silica gel: MS, m/z 600 M+ ; NMR (CDCl3, 200 MHz) δ 1.0 (t, OCH2CH2CH3), 1.82 (q, OCH2CH2CH3), 1.9-2.4(m, SO2CH2CH2CH2OH, H-4), 2.5(m, H-3), 3.58 (t, SO2CH2CH2CH2OH), 3.72(m, CH2OH), 3.86, 3.92(2s, 3 OCH3), 4.18 (t, OCH2CH2CH3), 5.18(s, OCH2Ar), 5.08-5.22 (m, H-2, H-5), 6.62(s, C5ArH), 7.28-7.54(m, ArH).
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[C:6]([NH:8][C:9]([C:11]2[N:23]([CH2:24][C:25]3[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=3)[C:14]3=[N:15][CH:16]=[C:17]([C:19]([F:22])([F:21])[F:20])[CH:18]=[C:13]3[CH:12]=2)=[O:10])[CH:5]=[CH:4][N:3]=1.Br[CH2:33][C:34](=O)[CH2:35][CH3:36]>C(#N)C>[CH2:35]([C:34]1[N:1]=[C:2]2[CH:7]=[C:6]([NH:8][C:9]([C:11]3[N:23]([CH2:24][C:25]4[CH:30]=[CH:29][CH:28]=[C:27]([F:31])[CH:26]=4)[C:14]4=[N:15][CH:16]=[C:17]([C:19]([F:22])([F:20])[F:21])[CH:18]=[C:13]4[CH:12]=3)=[O:10])[CH:5]=[CH:4][N:3]2[CH:33]=1)[CH3:36]
Reactant: CCC(=O)CBr
Reactant: Nc1cc(NC(=O)c2cc3cc(C(F)(F)F)cnc3n2Cc2cccc(F)c2)ccn1
Solvent: CC#N
Product: CCc1cn2ccc(NC(=O)c3cc4cc(C(F)(F)F)cnc4n3Cc3cccc(F)c3)cc2n1
Temperature: 150 °C
Yield: 54.4 %

Procedure:
0.125 g (0.29 mmol) of N-[2-aminopyrid-4-yl]-5-trifluoromethyl-1-[(3-fluorophenyl)-methyl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide, prepared according to the protocol described in step 15.2, 0.088 g (0.58 mmol) of 1-bromobutan-2-one and 4 mL of acetonitrile are placed in a 10 mL pressure tube specific for microwave reactors. The tube is then sealed and heated in the microwave reactor at 150° C. for two 1-hour cycles. After this time, the reaction mixture is concentrated under reduced pressure. The crude reaction product is then purified by chromatography on a column of silica gel, eluting with a mixture of dichloromethane and methanol. 0.076 g of the expected product is thus obtained in the form of a yellow solid.
Reaction SMILES: [CH:1]([C:3]1[C:4]([CH3:20])=[C:5]([NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:6]=[CH:7][CH:8]=1)=O.[N+:21]([CH2:24][CH3:25])([O-:23])=[O:22].C([O-])(=O)C.[NH4+]>C(O)(=O)C>[CH3:20][C:4]1[C:3](/[CH:1]=[C:24](/[N+:21]([O-:23])=[O:22])\[CH3:25])=[CH:8][CH:7]=[CH:6][C:5]=1[NH:9][C:10](=[O:19])[O:11][CH2:12][C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1
Reactant: CC[N+](=O)[O-]
Reactant: Cc1c(C=O)cccc1NC(=O)OCc1ccccc1
Agent: CC(=O)[O-]
Agent: [NH4+]
Solvent: CC(=O)O
Product: C/C(=C\c1cccc(NC(=O)OCc2ccccc2)c1C)[N+](=O)[O-]
Temperature: 25 °C
Reaction time: 3 h
Yield: 39.5 %

Procedure:
A solution of benzyl 3-formyl-2-methylphenylcarbamate (5.1667 g, 19.19 mmol), nitroethane (6.89 ml, 96 mmol) and ammonium acetate (7.39 g, 96 mmol) in acetic acid (Volume: 64.0 ml) under nitrogen was heated at 95° C. After 3 h, the reaction was cooled to room temperature and concentrated in vacuo. The residue was dissolved in water (40 mL) and CH2Cl2 (75 mL), and basified with Na2CO3 (s). The layers were separated, and the aqueous layer was extracted with CH2Cl2 (2×75 mL). The organic layers were combined, dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography using an ISCO 330 g column eluting with 50-100% hexane/CH2Cl2. Appropriate fractions were collected and concentrated in vacuo to give (E)-benzyl 2-methyl-3-(2-nitroprop-1-enyl)phenylcarbamate (2.4714 g, 39.5% yield) as a yellow solid, LC/MS (M+H)=327.16. 0.6875 g of desired product (75% pure by HPLC) was also collected.
Reaction SMILES: [C:1]1([Mg]Br)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.O1CCCC1.CS([C:18]1[CH:23]=[C:22]([C:24]2[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][N:25]=2)[N:21]2[N:34]=[CH:35][N:36]=[C:20]2[N:19]=1)(=O)=O>O>[C:1]1([C:18]2[CH:23]=[C:22]([C:24]3[CH:29]=[CH:28][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:26][N:25]=3)[N:21]3[N:34]=[CH:35][N:36]=[C:20]3[N:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CS(=O)(=O)c1cc(-c2ccc(C(F)(F)F)cn2)n2ncnc2n1
Reactant: Br[Mg]c1ccccc1
Solvent: C1CCOC1
Solvent: O
Product: FC(F)(F)c1ccc(-c2cc(-c3ccccc3)nc3ncnn23)nc1
Temperature: 0 °C
Reaction time: 0.08 h

Procedure:
0.2 mL of a phenyl magnesium bromide 3.0 M tetrahydrofuran solution was added at 0° C. to a tetrahydrofuran (dehydrated) 3 mL solution of 200 mg of 5-(methylsulfonyl)-7-(5-(trifluoromethyl)pyridin-2-yl)-[1,2,4]triazolo[1,5-a]pyrimidine, followed by stirring at 0° C. for 5 minutes. After completion of the reaction, water was added to the reaction liquid, followed by extraction with ethyl acetate, the organic layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=4/1) to obtain 93 mg of the desired product.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:10]=[C:9]([CH2:12][NH2:13])[O:8][C:7]=2[CH:14]=1.[CH2:15]([N:18]=[C:19]=[O:20])[CH2:16][CH3:17].[N-]=C=O>C1(C)C=CC=CC=1.O>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]2[O:11][CH:10]=[C:9]([CH2:12][NH:13][C:19]([NH:18][CH2:15][CH2:16][CH3:17])=[O:20])[O:8][C:7]=2[CH:14]=1
Reactant: CCCN=C=O
Reactant: COc1ccc2c(c1)OC(CN)=CO2
Agent: [N-]=C=O
Solvent: Cc1ccccc1
Solvent: O
Product: CCCNC(=O)NCC1=COc2ccc(OC)cc2O1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
The amine obtained in Step C of Example 24 is dissolved in 16 ml of anhydrous toluene; 0.78 g (9.17 mmol) of n-propyl isocyanate is then added to the medium. After 4 hours of stirring under an inert atmosphere and at ambient temperature, the excess of isocyanate is neutralised with a few drops of water. The solvent is then evaporated in vacuo. The residue obtained is purified on a silica column (eluant: MeOH/CH2Cl2: 10/90) to yield the title urea in the form of a white solid.
Reaction SMILES: [Si:1]([O:8][C@H:9]([CH2:24][O:25][Si:26]([C:29]([CH3:32])([CH3:31])[CH3:30])([CH3:28])[CH3:27])[C@@H:10]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[C:11]1SC=CN=1)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].FC(S(OC)(=O)=[O:38])(F)F.[BH4-].[Na+].O>CC#N.[Hg](Cl)Cl>[Si:1]([O:8][C@H:9]([CH2:24][O:25][Si:26]([C:29]([CH3:31])([CH3:30])[CH3:32])([CH3:27])[CH3:28])[C@@H:10]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:20])[CH3:21])[CH2:11][OH:38])([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N[C@@H](c1nccs1)[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Reactant: COS(=O)(=O)C(F)(F)F
Agent: Cl[Hg]Cl
Agent: [BH4-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: CC(C)(C)OC(=O)N[C@@H](CO)[C@@H](CO[Si](C)(C)C(C)(C)C)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 97.1 %

Procedure:
A solution of tert-butyl (1R,2S)-2,3-bis(tert-butyldimethylsilyloxy)-1-(thiazol-2-yl)propylcarbamate (6.150 g, 12.2 mmol) in 120 mL MeCN was treated with 4 A mol. sieves and was allowed to stir at room temperature for 10 minutes. Methyl trifluoromethylsulfonate (1.62 ml, 14.7 mmol) was added, and the reaction mixture was allowed to stir for an additional 30 minutes. The reaction mixture was then concentrated in vacuo. The crude residue was dissolved in 100 mL MeOH, cooled to 0° C., and treated with NaBH4 (1.39 g, 36.7 mmol). The reaction mixture was allowed to warm to RT and stir for an additional 20 minutes. The reaction mixture was then concentrated, diluted with EtOAc, filtered through celite and again concentrated in vacuo. The residue was dissolved in 100 mL ACN and 20 mL water and was treated with mercury(II)chloride (3.32 g, 12.2 mmol). After stirring for 30 minutes, an additional portion of NaBH4 (1.39 g, 36.7 mmol) was added, and the reaction mixture was allowed to stir for another 30 minutes. The reaction mixture was quenched with saturated NaHCO3 solution and diluted with EtOAc. The crude reaction mixture was then washed with water then brine. The organic layer was dried over MgSO4 and concentrated in vacuo. The crude residue was forced through a short plug of silica eluting with ether. The filtrate was again concentrated in vacuo yielding tert-butyl (2S,3S)-3,4-bis(tert-butyldimethylsilyloxy)-1-hydroxybutan-2-ylcarbamate (5.33 g, 96.9% yield) with minor impurities.
Reaction SMILES: BrBr.[CH3:3][N:4]1[C:8]([CH2:9][O:10][C:11]2[CH:17]=[CH:16][C:14]([NH2:15])=[CH:13][CH:12]=2)=[CH:7][C:6]([CH3:18])=[N:5]1.[S-:19][C:20]#[N:21].[K+].C(=O)([O-])[O-].[K+].[K+]>C(O)(=O)C.O>[CH3:3][N:4]1[C:8]([CH2:9][O:10][C:11]2[CH:17]=[CH:16][C:14]3[N:15]=[C:20]([NH2:21])[S:19][C:13]=3[CH:12]=2)=[CH:7][C:6]([CH3:18])=[N:5]1
Reactant: N#C[S-]
Reactant: Cc1cc(COc2ccc(N)cc2)n(C)n1
Agent: BrBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)O
Solvent: O
Product: Cc1cc(COc2ccc3nc(N)sc3c2)n(C)n1
Yield: 80.6 %

Procedure:
add, dropwise, a solution of 0.103 cm3 of dibromine in 3 cm3 of glacial acetic acid at around 20° C. to a solution of 0.44 g of 4-[(1,3-dimethyl-1H-pyrazol-5-yl)methoxy]aniline and 0.787 g of potassium thiocyanate in 6 cm3 of glacial acetic acid. After stirring for about twenty hours, the reaction mixture is poured into 50 cm3 of water. The pH of the solution obtained is adjusted to 8-9 by adding solid potassium carbonate. A gum forms. After stirring for about an hour, the beige solid that formed is drained, washed three times with 20 cm3 of water, then dried in a desiccator under reduced pressure (0.2 kPa) in the presence of phosphoric anhydride. We obtain 0.448 g of 6-[(1,3-dimethyl-1H-pyrazol-5-yl)methoxy]-1,3-benzothiazol-2-amine in the form of a beige powder, which has the following characteristics:
Reaction SMILES: N1C=CN=C1.[C:6]([Si:10]([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)Cl)([CH3:9])([CH3:8])[CH3:7].[Br:24][C:25]1[CH:26]=[C:27]([CH2:32][OH:33])[CH:28]=[C:29]([F:31])[CH:30]=1.O>CN(C)C=O>[Br:24][C:25]1[CH:26]=[C:27]([CH:28]=[C:29]([F:31])[CH:30]=1)[CH2:32][O:33][Si:10]([C:6]([CH3:9])([CH3:8])[CH3:7])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: OCc1cc(F)cc(Br)c1
Reactant: CC(C)(C)[Si](Cl)(c1ccccc1)c1ccccc1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)[Si](OCc1cc(F)cc(Br)c1)(c1ccccc1)c1ccccc1
Temperature: 25 °C
Yield: 87.8 %

Procedure:
Imidazole (3.3 g) and tert-butyl-diphenylchlorosilane (10.0 g) were added to a solution of (3-bromo-5-fluorophenyl)methanol (5.0 g) in dimethylformamide (50 ml), and the mixture was stirred over night at room temperature. The reaction mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with saturated saline solution and dried over anhydrous magnesium sulfate. After filtration, the solvent was evaporated from the filtrate under reduced pressure to give the residue. The resulting residue was purified by silica gel column chromatography (n-hexane-ethyl acetate) to obtain [(3-bromo-5-fluorobenzyl)oxy] (tert-butyl)diphenylsilane (9.5 g).
Reaction SMILES: [OH:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:17]=[CH:18][C:19]=1[O:20][CH3:21])[CH2:7][CH:8]([C:13]([O:15][CH3:16])=[O:14])[C:9]([O:11][CH3:12])=[O:10].[C:22]1([N:28]=[C:29]=[O:30])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1>>[NH:28]([C:29]([O:1][CH2:2][CH2:3][C:4]1[CH:5]=[C:6]([CH:17]=[CH:18][C:19]=1[O:20][CH3:21])[CH2:7][CH:8]([C:9]([O:11][CH3:12])=[O:10])[C:13]([O:15][CH3:16])=[O:14])=[O:30])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1
Reactant: COC(=O)C(Cc1ccc(OC)c(CCO)c1)C(=O)OC
Reactant: O=C=Nc1ccccc1
Product: COC(=O)C(Cc1ccc(OC)c(CCOC(=O)Nc2ccccc2)c1)C(=O)OC

Procedure:
Using dimethyl 2-[3-(2-hydroxyethyl)-4-methoxybenzyl]malonate and phenylisocyanate, the title compound was obtained in the same manner as described in Example 192b).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([Cl:12])[C:5]([O:10][CH3:11])=[C:6]([CH:9]=1)[CH:7]=[O:8].[CH3:13][Mg]Br>C(OCC)C>[F:1][C:2]1[CH:3]=[C:4]([Cl:12])[C:5]([O:10][CH3:11])=[C:6]([CH:7]([OH:8])[CH3:13])[CH:9]=1
Reactant: COc1c(Cl)cc(F)cc1C=O
Reactant: C[Mg]Br
Solvent: CCOCC
Product: COc1c(Cl)cc(F)cc1C(C)O
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 98 %

Procedure:
To a stirred solution of 5-Fluoro-2-methoxy-3-chlorobenzaldehyde (2.0 g, 11.0 mmol) in dry diethyl ether (40 mL) at 0° C. was added methylmagnesium bromide of 3.0 M in ether (8.8 mL, 27.12 mmol). The reaction mixture was brought to room temperature and was stirred for 30 min. then refluxed for 3 hours. It was then cooled to 0° C. and quenched by adding saturated aqueous NH4Cl. The two liquid layers were separated. The aqueous layer was extracted with ether. The combined organic layers were washed with water, dried, and concentrated to the crude compound which was purified by silica gel column (10-25% ethyl acetate in hexanes) to afford 1-(5-Fluoro-2-methoxy-3-chlorophenyl)ethanol (2.1 g, 98%): 1H NMR (400 MHz, CDCl3): δ 7.12 (dd, 1H), 7.04 (dd, 1H), 5.19 (m, 1H), 3.84 (s, 3H), 2.18 (bs, 1H), 1.43 (d, 3H).
Reaction SMILES: [CH3:1][C:2]([O-:5])(C)[CH3:3].[K+].O[C:8]1[CH:16]=[CH:15]C=[C:13]2[C:9]=1[CH2:10][CH2:11][C:12]2=O>CCOCC>[CH:10](=[C:9]1[C:8]2[CH:16]=[CH:15][CH:3]=[C:2]([OH:5])[C:1]=2[CH2:12][CH2:13]1)[CH3:11]
Reactant: CC(C)(C)[O-]
Reactant: O=C1CCc2c(O)cccc21
Agent: [K+]
Solvent: CCOCC
Product: CC=C1CCc2c(O)cccc21
Reaction time: 0.25 h
Yield: 17.1 %

Procedure:
To a suspension of CH3CH2PPh3I (677 mg, 1.62 mmol) in Et2O (10 mL) was added t-BuOK (181 mg, 1.62 mmol). The mixture was stirred for 15 minutes, to which was added dropwise 4-hydroxy-indan-1-one (200 mg, 1.35 mmol). The mixture was stirred at room temperature overnight and then diluted with diethylether. The mixture was filtered on a pad of celite, and the filtrate was concentrated. The crude residue was purified by column chromatography to give 1-ethylidene-indan-4-ol (37 mg, 17%).
Reaction SMILES: [CH3:1][CH:2]1[CH2:7][CH2:6][C:5](=O)[CH2:4][CH2:3]1.C1CCCCC1.Cl.[Br:16][C:17]1[CH:22]=[CH:21][C:20]([NH:23]N)=[CH:19][CH:18]=1>C(O)(=O)C>[Br:16][C:17]1[CH:22]=[C:21]2[C:20](=[CH:19][CH:18]=1)[NH:23][C:5]1[CH2:6][CH2:7][CH:2]([CH3:1])[CH2:3][C:4]2=1
Reactant: CC1CCC(=O)CC1
Reactant: NNc1ccc(Br)cc1
Agent: Cl
Solvent: CC(=O)O
Solvent: C1CCCCC1
Product: CC1CCc2[nH]c3ccc(Br)cc3c2C1
Yield: 74.2 %

Procedure:
To a solution of 4-methylcyclohexanone (5.47 mL, 44.6 mmol), cyclohexane (70 mL) and glacial acetic acid (50 mL) was added 4-bromophenylhydrazine hydrochloride (10.0 g, 44.6 mmol) and the reaction mixture was refluxed for 23 h under a nitrogen atmosphere. The cooled reaction mixture was filtered and the filtrate was evaporated. Diethyl ether was added and the mixture was washed with a saturated sodium bicarbonate solution and then water; the ether solution was dried and evaporated. The crude product was recrystallised from ethanol over an ice bath, filtered, washed with cold PS and dried in vacuo to afford 6-bromo-3-methyl-1,2,3,4-tetrahydrocarbazole (8.73 g, 33.1 mmol, 74%) as an off-white solid, mp 108-110° C.
Reaction SMILES: [CH3:1][N:2](S(C1C=CC=CC=1)(=O)=O)[N:3]=[C:4](Cl)[C:5]1[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=1[Cl:12].[C:23]([C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[C:29]([O:35][CH2:36][CH3:37])[CH:28]=1)([CH3:26])([CH3:25])[CH3:24].[Cl-].[Al+3].[Cl-].[Cl-].ClC1C=CC=CC=1Cl>C(Cl)(Cl)Cl>[C:23]([C:27]1[CH:34]=[CH:33][C:30]([C:31]2[N:2]([CH3:1])[N:3]=[C:4]([C:5]3[C:10]([F:11])=[CH:9][CH:8]=[CH:7][C:6]=3[Cl:12])[N:32]=2)=[C:29]([O:35][CH2:36][CH3:37])[CH:28]=1)([CH3:26])([CH3:24])[CH3:25]
Reactant: CCOc1cc(C(C)(C)C)ccc1C#N
Reactant: CN(N=C(Cl)c1c(F)cccc1Cl)S(=O)(=O)c1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClC(Cl)Cl
Solvent: Clc1ccccc1Cl
Product: CCOc1cc(C(C)(C)C)ccc1-c1nc(-c2c(F)cccc2Cl)nn1C
Temperature: 140 °C
Reaction time: 0.5 h
Yield: 11.6 %

Procedure:
A mixture of N-methyl-N-(benzenesulfonyl)-2-chloro-6-fluorobenzohydrazonoyl chloride (1.60 g), 4-t-butyl-2-ethoxybenzonitrile (1.00 g), anhydrous aluminum chloride (0.60 g) and o-dichlorobenzene (5 ml) is stirred at an oil bath temperature of 140° C. for 30 minutes. After cooling, the reaction mixture is dissolved in chloroform (100 ml), washed with dilute hydrochloric acid, dilute aqueous solution of sodium hydroxide and saline in this order, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The concentrate is purified by silica gel column chromatography using mixed solvent of hexane-ethyl acetate as eluent to give 0.20 g of desired compound (melting point: 108.0°-111.0° C.).