Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: S1C=CC(CC=[O:8])=C1.[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH:16](O)[CH3:17]>C(Cl)Cl.CCOCC>[Cl:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[CH2:16][CH:17]=[O:8]
Reactant: O=CCc1ccsc1
Reactant: CC(O)c1ccccc1Cl
Solvent: CCOCC
Solvent: ClCCl
Product: O=CCc1ccccc1Cl

Procedure:
The title compound is prepared as described in Example 12 (Procedure B) for 3-thiophenylacetaldehyde but using 2-chlorophenyl-ethanol. The title compound: ES-MS: 152.9 [M−H]−; single peak at tR=3.82 min (System 2); Rf=0.70 (CH2Cl2/Et2O, 95/5).
Reaction SMILES: [CH2:1]([N:3]([CH2:6][CH3:7])[CH2:4]C)C.[CH3:8][O:9][C:10]1[CH:11]=C([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])CO.CS(Cl)(=O)=O.Cl.CNC>C(Cl)Cl>[CH3:8][O:9][C:10]1[CH:11]=[C:7]([CH:15]=[CH:16][C:17]=1[N+:18]([O-:20])=[O:19])[CH2:6][N:3]([CH3:1])[CH3:4]
Reactant: CCN(CC)CC
Reactant: COc1cc(CO)ccc1[N+](=O)[O-]
Agent: CNC
Agent: CS(=O)(=O)Cl
Agent: Cl
Solvent: ClCCl
Product: COc1cc(CN(C)C)ccc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 1 h
Yield: 65 %

Procedure:
Triethylamine (5 mL) was added to a solution of 3-methoxy-4-nitrobenzyl alcohol (2.5 g, 13.6 mmol) in 50 mL of methylene chloride, and the mixture was cooled to 0° C. under nitrogen. Methanesulfonyl chloride (1.9 g, 16.3 mmol) was added dropwise and the mixture stirred at this temperature for 1 hour. Triethylamine (5 mL) was added, followed by dimethylamine hydrochloride (1.6 g, 20.4 mmol). After 5 minutes, the cooling bath was removed, and the mixture stirred at ambient temperature for 2.5 hours. The mixture was diluted with methylene chloride (75 mL) and washed with water (3×75 mL), and extracted into dilute aqueous HCl (3×75 mL). The combined aqueous extracts were washed with methylene chloride (3×75 mL), basified (3N NaOH), and extracted into methylene chloride (3×75 mL). The combined organic extracts were washed with water (3×75 mL), dried (MgSO4), and evaporated, providing 1.8 g of the product, in 65% yield: 1H NMR (CDCl3) δ 2.26 (s, 6H), 3.45 (s, 2H), 3.97 (s, 3H), 6.95 (d, J=8.2 Hz, 1H), 7.12 (s, 1H), 7.82 (d, J=8.2 Hz, 1H).
Reaction SMILES: CO[C:3](=[O:17])[C:4]1[CH:13]=[C:12]([N+:14]([O-:16])=[O:15])[CH:11]=[C:6]([C:7]([O:9]C)=O)[CH:5]=1.[CH2:18]([CH2:20][NH2:21])[OH:19]>CO>[OH:19][CH2:18][CH2:20][NH:21][C:7]([C:6]1[CH:11]=[C:12]([N+:14]([O-:16])=[O:15])[CH:13]=[C:4]([C:3]([NH:21][CH2:20][CH2:18][OH:19])=[O:17])[CH:5]=1)=[O:9]
Reactant: COC(=O)c1cc(C(=O)OC)cc([N+](=O)[O-])c1
Reactant: NCCO
Solvent: CO
Product: O=C(NCCO)c1cc(C(=O)NCCO)cc([N+](=O)[O-])c1
Yield: 67.3 %

Procedure:
A solution containing dimethyl-5-nitroisophthalate (23.9 g, 100 mmol) and ethanolamine (13.4 g, 220 mmol) in methanol (300 mL) was refluxed for 48 hours. The solvent was removed by evaporation under reduced pressure. The crude product was purified by crystallization from EtOAC:MeOH 1 ml v/v) to afford 20.0 g of pure N,N′-bis(2-hydroxyethyl)-5-nitro-1,3-benzenedicarboxamide as white crystals. m.p.=151.3-151.4° C., uncorrected
Reaction SMILES: [CH3:1][O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:31](=[O:32])[C:13]3=[C:14]([C:22]4[CH:27]=[CH:26][C:25]([N+:28]([O-])=O)=[CH:24][CH:23]=4)[NH:15][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=4[C:12]3=[N:11]2)=[CH:6][CH:5]=1.C(O)(=O)C>C(O)C.CN(C=O)C.[Pd]>[CH3:1][O:2][C:3](=[O:33])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:31](=[O:32])[C:13]3=[C:14]([C:22]4[CH:27]=[CH:26][C:25]([NH2:28])=[CH:24][CH:23]=4)[NH:15][C:16]4[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=4[C:12]3=[N:11]2)=[CH:6][CH:5]=1
Reactant: COC(=O)c1ccc(-n2nc3c4ccccc4[nH]c(-c4ccc([N+](=O)[O-])cc4)c-3c2=O)cc1
Agent: [Pd]
Solvent: CN(C)C=O
Solvent: CC(=O)O
Solvent: CCO
Product: COC(=O)c1ccc(-n2nc3c4ccccc4[nH]c(-c4ccc(N)cc4)c-3c2=O)cc1
Yield: 82.6 %

Procedure:
4-[4-(4-Nitro-phenyl)-3-oxo-3,5-dihydro-pyrazolo[4,3-c]quinolin-2-yl]-benzoic acid methyl ester (2.6 g, 5.9 mmol) and Pd/C (100 mg, 10%) were suspended in ethanol (150 mL) and acetic acid (6 mL) and stirred under hydrogen for 24 h. The resulting yellow-orange suspension was diluted with DMF (50 mL) and filtered. The solvent was removed in vacuo to leave a residue which was washed with methanol to give 4-[4-(4-amino-phenyl)-3-oxo-3,5-dihydro-pyrazolo[4,3-c]quinolin-2-yl]-benzoic acid methyl ester (2.0 g, 82%) as a pale orange solid, LCMS m/z 411.39 [M+H]+ @ RT 1.27 min, 79% purity.
Reaction SMILES: [C:1]([O:5][C:6](=[O:22])[CH2:7][N:8]=[C:9]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)([CH3:4])([CH3:3])[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].Br[CH2:34][CH2:35][CH:36]=[CH2:37]>C1COCC1>[C:1]([O:5][C:6](=[O:22])[CH:7]([N:8]=[C:9]([C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)[C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=1)[CH2:37][CH2:36][CH:35]=[CH2:34])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)CN=C(c1ccccc1)c1ccccc1
Reactant: C=CCCBr
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Na+]
Solvent: C1CCOC1
Product: C=CCCC(N=C(c1ccccc1)c1ccccc1)C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 94.1 %

Procedure:
While under a nitrogen atmosphere a stirred solution of (benzhydrylidene-amino)-acetic acid tert-butyl ester (5 g, 16.9 mmol) in THF (80 mL, 0.2 M) was carefully treated with sodium bis(trimethylsilyl)amide (18.6 mL, 1.0 M, 1.1 equiv) at −78° C. After stirring for 30 min, 4-bromo-but-1-ene (2.1 mL, 20.3 mmol, 1.2 equiv) was slowly added. The cooling bath was removed and the reaction mixture gradually warmed to room temperature and stirred for overnight. The solution was cooled to 0° C. and quenched with water. The resulting solution was diluted with ethyl acetate and washed successively with water and saturated aqueous NaCl, dried over MgSO4, filtered and concentrated. Purification by MPLC (1-25% ethyl acetate in heptane) gave 2-(benzhydrylidene-amino)-hex-5-enoic acid tert-butyl ester as colorless oil (5.6 g, 15.9 mmol, 94%).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][NH:12][C:13]2[CH:19]=[CH:18][C:17]([C:20]3[O:21][C:22]4[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=4[N:24]=3)=[CH:16][C:14]=2[NH2:15])=[CH:7][CH:6]=1)=[O:4].Cl.[C:30](=N)(OC)[CH3:31].C(=O)([O-])O.[Na+]>CO>[O:21]1[C:22]2[CH:28]=[CH:27][CH:26]=[CH:25][C:23]=2[N:24]=[C:20]1[C:17]1[CH:18]=[CH:19][C:13]2[N:12]([CH2:11][C:8]3[CH:7]=[CH:6][C:5]([C:3]([O:2][CH3:1])=[O:4])=[CH:10][CH:9]=3)[C:30]([CH3:31])=[N:15][C:14]=2[CH:16]=1
Reactant: COC(C)=N
Reactant: COC(=O)c1ccc(CNc2ccc(-c3nc4ccccc4o3)cc2N)cc1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1ccc(Cn2c(C)nc3cc(-c4nc5ccccc5o4)ccc32)cc1
Temperature: 25 °C
Yield: 98.4 %

Procedure:
To a solution of 2-(2-(4-methoxycarbonylphenylmethyl)aminoanilin-5-yl)benzoxazole (see Working Example 113-2) (59.0 mg, 0.159 mmol) in methanol (3 mL) was added methyl acetimidate hydrochloride (19 mg, 0.174 mmol), and this was heated to reflux for 1.5 hours. After the reaction was complete, saturated aqueous sodium hydrogen carbonate solution was added, and this was stirred for several minutes at room temperature. The crystals obtained were filtered, and after being washed with water, they were dried to yield the title compound (62.2 mg, 98% yield) as yellow crystals.
Reaction SMILES: [Br:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[N:20]=[C:21]([CH3:24])[S:22][CH:23]=3)[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-])=O)[C:5]([NH2:8])=[N:6][CH:7]=1.CCO.[N:28]1([CH2:33][C:34]2[CH:41]=[CH:40][C:37]([CH:38]=O)=[CH:36][CH:35]=2)[CH:32]=[CH:31][CH:30]=[N:29]1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(Cl)Cl.N.CN(C=O)C>[N:28]1([CH2:33][C:34]2[CH:41]=[CH:40][C:37]([C:38]3[NH:8][C:5]4=[N:6][CH:7]=[C:2]([Br:1])[C:3]([N:12]5[CH2:17][CH2:16][N:15]([CH2:18][C:19]6[N:20]=[C:21]([CH3:24])[S:22][CH:23]=6)[CH2:14][CH2:13]5)=[C:4]4[N:9]=3)=[CH:36][CH:35]=2)[CH:32]=[CH:31][CH:30]=[N:29]1
Reactant: Cc1nc(CN2CCN(c3c(Br)cnc(N)c3[N+](=O)[O-])CC2)cs1
Reactant: O=Cc1ccc(Cn2cccn2)cc1
Agent: N
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CCO
Solvent: ClCCl
Solvent: CN(C)C=O
Product: Cc1nc(CN2CCN(c3c(Br)cnc4[nH]c(-c5ccc(Cn6cccn6)cc5)nc34)CC2)cs1
Temperature: 85 °C

Procedure:
To a mixture of 5-bromo-4-(4-((2-methylthiazol-4-yl)methyl)piperazin-1-yl)-3-nitropyridin-2-amine (0.050 g, 0.12 mmol), EtOH (2.3 mL) and DMF (0.2 mL), 4-(1H-pyrazol-1-ylmethyl)-benzaldehyde (0.025 g, 0.13 mmol) was added followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.36 mL, 0.36 mmol). The reaction mixture was heated at 85° C. for 24 h, then allowed to cool to room temperature and diluted with DCM and a few drops of aqueous NH3 until complete dissolution was observed. This solution was deposited on two preparative silica TLC plates and eluted with DCM/MeOH (v/v; 96:4). The title compound was obtained after trituration with ether as a white solid (0.033 g, 49%); 1H-NMR (500 Mz, DMSO-d6): δ 2.62-2.70 (m, 7H), 3.64 (s, 2H, NCH2), 3.65-3.70 (m, 4H), 5.42 (s, 2H, NCH2), 6.30 (t, J=2.5 Hz, 1H), 7.32 (s, 1H, thiazole 5-H), 7.34 (d, J=8.0 Hz, 1H), 7.48-7.51 (m, 1H), 7.86 (d, J=2.0 Hz, 1H), 8.13 (d, J=8.0 Hz, 2H), 8.23 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.49 (br s, 1H, imidazo[4,5-b]pyridine N—H); LC (Method B)-MS (ESI, m/z) 3.17 min—549/551 [(M+H)+, Br isotopic pattern]. ESI-HRMS: Found: 549.1176, calculated for C25H26N8SBr (M+H)+: 549.1185.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=[O:15])=[C:12]([CH:16]([CH3:18])[CH3:17])[C:11]([CH2:19][OH:20])=[C:10]([CH:21]([CH3:23])[CH3:22])[N:9]=2)=[CH:4][CH:3]=1.[CH3:24]O>>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([CH:14]=[O:15])=[C:12]([CH:16]([CH3:18])[CH3:17])[C:11]([CH2:19][O:20][CH3:24])=[C:10]([CH:21]([CH3:23])[CH3:22])[N:9]=2)=[CH:4][CH:3]=1
Reactant: CC(C)c1nc(-c2ccc(F)cc2)c(C=O)c(C(C)C)c1CO
Reactant: CO
Product: COCc1c(C(C)C)nc(-c2ccc(F)cc2)c(C=O)c1C(C)C

Procedure:
3.15 g (96% of theory) of colorless crystals of m.p. 77° C. (from MeOH) are obtained from 3.15 g (10 mmol) of the compound from Example 122 in analogy to the instructions from Example 59
Reaction SMILES: [CH2:1]([O:8][CH2:9][C@H:10]([CH:34]([CH3:36])[CH3:35])[CH2:11][C@H:12]([NH:26][C:27](=[O:33])[O:28][C:29]([CH3:32])([CH3:31])[CH3:30])[C@@H:13]([OH:25])[CH2:14][NH:15][C:16](=[O:24])[C:17]([CH3:23])([CH3:22])[CH2:18][CH2:19][CH2:20][CH3:21])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CO[C:39](OC)([CH3:41])[CH3:40]>CC(C)=O>[CH2:1]([O:8][CH2:9][C@H:10]([CH:34]([CH3:35])[CH3:36])[CH2:11][C@H:12]1[C@@H:13]([CH2:14][NH:15][C:16](=[O:24])[C:17]([CH3:22])([CH3:23])[CH2:18][CH2:19][CH2:20][CH3:21])[O:25][C:39]([CH3:41])([CH3:40])[N:26]1[C:27]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COC(C)(C)OC
Reactant: CCCCC(C)(C)C(=O)NC[C@H](O)[C@H](C[C@H](COCc1ccccc1)C(C)C)NC(=O)OC(C)(C)C
Solvent: CC(C)=O
Product: CCCCC(C)(C)C(=O)NC[C@H]1OC(C)(C)N(C(=O)OC(C)(C)C)[C@H]1C[C@H](COCc1ccccc1)C(C)C
Temperature: 0 °C
Reaction time: 2 h
Yield: 73.2 %

Procedure:
To a solution of tert-butyl (2S,3S,5S)-5-(benzyloxymethyl)-1-(2,2-dimethylhexanamido)-2-hydroxy-6-methylheptan-3-ylcarbamate (3.8 g, 7.5 mmol) in acetone (50 mL) was added 2,2-dimethoxy-propane (6.0 g, 57.7 mmol). The resulting mixture was cooled to 0° C., BF3Et2O (100 mg, 0.7 mmol) was added. The reaction mixture was allowed to warm to rt and stirred for 2 h. TLC showed the starting material had been consumed. The reaction mixture was quenched with Et3N. The solvent was removed in vacuo and the residue was partitioned between water and EtOAc. The organic layers were washed with H2O and brine, dried over Na2SO4, and evaporated to produce (4S,5R)-tert-butyl 4-((S)-2-(benzyloxymethyl)-3-methylbutyl)-5-((2,2-dimethylhexanamido)methyl)-2,2-dimethyloxazolidine-3-carboxylate (3.0 g, 73%); MS: 547 (M++1).
Reaction SMILES: [NH2:1][C:2](=[C:10]([C:15](=O)[CH:16]([CH3:18])[CH3:17])[C:11]([O:13][CH3:14])=[O:12])[C:3]1[CH:8]=[CH:7][C:6]([F:9])=[CH:5][CH:4]=1.C1(C)C=CC=CC=1.[C:27]([N:29]([CH3:34])[S:30]([CH3:33])(=[O:32])=[O:31])#[N:28]>[Ti](Cl)(Cl)(Cl)Cl.O>[F:9][C:6]1[CH:7]=[CH:8][C:3]([C:2]2[C:10]([C:11]([O:13][CH3:14])=[O:12])=[C:15]([CH:16]([CH3:18])[CH3:17])[N:28]=[C:27]([N:29]([S:30]([CH3:33])(=[O:32])=[O:31])[CH3:34])[N:1]=2)=[CH:4][CH:5]=1
Reactant: CN(C#N)S(C)(=O)=O
Reactant: COC(=O)C(C(=O)C(C)C)=C(N)c1ccc(F)cc1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: O
Solvent: Cc1ccccc1
Product: COC(=O)c1c(-c2ccc(F)cc2)nc(N(C)S(C)(=O)=O)nc1C(C)C
Temperature: 110 °C
Reaction time: 4.5 h
Yield: 80.3 %

Procedure:
10.0 g (37.7 mmol) of methyl 2-[1-amino-1-(4-fluorophenyl)methylene]-4-methyl-3-oxopentanoate were introduced into 50 ml of toluene together with 10.17 g (75.4 mmol) of N-cyano-N-methylmethanesulphonamide and the mixture was treated at room temperature with 3.61 g (18.9 mmol) of titanium tetrachloride. The reaction progressed exothermically. The red-orange-coloured suspension was heated to 110° C. and stirred for 4.5 h. It was then cooled to room temperature and treated with 30 ml of water. The organic phase was separated off and the aqueous phase was extracted with ethyl acetate (30 ml). The combined organic phases were washed with 30 ml of water and dried over magnesium sulphate. After filtering and concentrating the solution in a water-jet vacuum and drying in vacuo, 11.54 g of crude product were obtained in the form of a tacky oil.
Reaction SMILES: [O:1]=[C:2]1[N:6]([CH2:7][OH:8])[C:5](=[O:9])[CH2:4][N:3]1[CH2:10][C:11]#[CH:12].C(N(CC)CC)C.[Cl:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=1[NH:31][CH:32]([CH:36]([CH3:38])[CH3:37])[C:33](O)=[O:34]>CCOCC>[Cl:20][C:21]1[CH:26]=[C:25]([C:27]([F:30])([F:29])[F:28])[CH:24]=[CH:23][C:22]=1[NH:31][CH:32]([CH:36]([CH3:38])[CH3:37])[C:33]([O:8][CH2:7][N:6]1[C:5](=[O:9])[CH2:4][N:3]([CH2:10][C:11]#[CH:12])[C:2]1=[O:1])=[O:34]
Reactant: C#CCN1CC(=O)N(CO)C1=O
Reactant: CC(C)C(Nc1ccc(C(F)(F)F)cc1Cl)C(=O)O
Solvent: CCOCC
Solvent: CCN(CC)CC
Product: C#CCN1CC(=O)N(COC(=O)C(Nc2ccc(C(F)(F)F)cc2Cl)C(C)C)C1=O
Reaction time: 0.5 h

Procedure:
To a stirred solution of (2,4-dioxo-1-propargyl-3-imidazolidinyl)methanol (0.99 mmol) and triethylamine (1.38 mmol) in ether (about 15 ml), under nitrogen, is added by syringe a solution of the acid chloride of 2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoic acid (1.5 mmol) in ether. The mixture is stirred for 30 minutes and then quenched with saturated aqueous sodium bicarbonate. The ether phase is washed with aqueous sodium bicarbonate, water and brine and filtered through silica. Evaporation of solvent, followed by thin layer chromatography using a circular chromatograph, eluting with 20% ether/hexane, gives (2,4-dioxo-1-propargyl-3-imidazolidinyl)methyl 2-(2-chloro-4-trifluoromethylphenylamino)-3-methylbutanoate.
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][CH:3]=1.[CH3:10][C:11]([CH3:13])=[O:12]>[OH-].[Na+]>[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[CH:10][C:11](=[O:12])[CH3:13])=[CH:4][CH:3]=1
Reactant: CC(C)=O
Reactant: O=Cc1ccc(O)cc1
Agent: [Na+]
Agent: [OH-]
Product: CC(=O)C=Cc1ccc(O)cc1
Yield: 70.4 %

Procedure:
4-Hydroxybenzaldehyde (10 g, 82 mmol) was dissolved in 28 ml of 10% sodium hydroxide aqueous solution, then acetone (20 ml) and 10% sodium hydroxide aqueous solution (40 ml) was added under stirring, and the reaction mixture was stirred for 6 hr at room temperature. separated solid diluted with water until all separated solid dissolved. The reaction mixture was neutralized with hydrochloric acid to pH=7.0. The precipitated solid was collected by filtration and washed with water and ethanol successively. The crude product was recrystallized from ethanol to give 9.3 g of a pale yellow solid, mp: 104-105° C., yield: 70.4%.
Reaction SMILES: [C:1]([OH:10])(=[O:9])[C:2]1[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[Cl:11][S:12]([OH:15])(=O)=[O:13]>O>[Cl:11][S:12]([C:5]1[CH:6]=[C:7]([S:12]([Cl:11])(=[O:15])=[O:13])[CH:8]=[C:2]([C:1]([OH:10])=[O:9])[C:3]=1[OH:4])(=[O:15])=[O:13]
Reactant: O=C(O)c1ccccc1O
Reactant: O=S(=O)(O)Cl
Solvent: O
Product: O=C(O)c1cc(S(=O)(=O)Cl)cc(S(=O)(=O)Cl)c1O

Procedure:
Salicylic acid (10 g) was added to chlorosulphonic acid (60 ml) during 5 minutes. The mixture was then heated at 130°-140° C. for 90 minutes. After cooling, the mixture was cooled and then added dropwise to an excess of a mixture of ice and water, keeping the temperature below 0° C. The precipitated solid was extracted with dichloromethane, and the organic extract was dried over sodium sulphate, and concentrated in vacuo to a small volume and treated with petroleum ether (b.p. 40°-60° C.). The precipitate was filtered off and recrystallized from a large volume of toluene to give 3,5-bis(chlorosulphonyl)salicylic acid (9.95 g), m.p. 185°-187° C.
Reaction SMILES: Br[C:2]1[S:6][C:5]([N:7]2[CH:11]=[CH:10][N:9]=[C:8]2[CH3:12])=[CH:4][CH:3]=1.[Li]CCCC.[CH2:18]([Sn:22](Cl)([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:23][CH2:24][CH2:25][CH3:26])[CH2:19][CH2:20][CH3:21].[NH4+].[Cl-]>C1COCC1>[CH3:12][C:8]1[N:7]([C:5]2[S:6][C:2]([Sn:22]([CH2:23][CH2:24][CH2:25][CH3:26])([CH2:27][CH2:28][CH2:29][CH3:30])[CH2:18][CH2:19][CH2:20][CH3:21])=[CH:3][CH:4]=2)[CH:11]=[CH:10][N:9]=1
Reactant: CCCC[Sn](Cl)(CCCC)CCCC
Reactant: Cc1nccn1-c1ccc(Br)s1
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Product: CCCC[Sn](CCCC)(CCCC)c1ccc(-n2ccnc2C)s1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 275.8 %

Procedure:
To the solution of 1-(5-bromothiophen-2-yl)-2-methyl-1H-imidazole (2 g, 8.3 mmol) in dried THF was added dropwise n-BuLi (2.5 M in hexane, 4 mL, 10 mmol) at −78° C., the mixture was stirred at −78° C. for 30 min. A solution of tributyltin chloride (4.6 g, 0.96 mmol) in THF was added dropwise, the solution was stirred at −78° C. for 1 hour, and the reaction solution was allowed to warm to room temperature and stirred for 1 hour. The reaction solution was poured into NH4Cl aqueous solution, the mixture was extracted with EtOAc (100 mL×3). The organic layer was washed with brine, dried over Na2SO4, then concentrated under reduced pressure, and the residue was purified by column chromatography to give 2-methyl-1-(5-(tributylstannyl)thiophen-2-yl)-1H-imidazole as a yellow oil (1.2 g, yield 31.8%).
Reaction SMILES: Cl.[C:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][N:13]=[N+]=[N-])=[CH:8][C:7]=1[NH:16][C:17](=[O:35])[CH2:18][CH:19]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[O:33][CH3:34])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])([CH3:5])([CH3:4])[CH3:3]>CC(C)=O.[Zn]>[C:2]([C:6]1[CH:11]=[CH:10][C:9]([CH2:12][NH2:13])=[CH:8][C:7]=1[NH:16][C:17](=[O:35])[CH2:18][CH:19]([C:25]1[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][C:26]=1[O:33][CH3:34])[CH2:20][CH2:21][CH2:22][CH2:23][CH3:24])([CH3:3])([CH3:4])[CH3:5]
Reactant: CCCCCC(CC(=O)Nc1cc(CN=[N+]=[N-])ccc1C(C)(C)C)c1ccc(OC)cc1OC
Agent: Cl
Agent: [Zn]
Solvent: CC(C)=O
Product: CCCCCC(CC(=O)Nc1cc(CN)ccc1C(C)(C)C)c1ccc(OC)cc1OC
Reaction time: 1 h
Yield: 87.3 %

Procedure:
301 mg (4.60 mmol) of zinc dust and then 5 ml of 2N aqueous hydrochloric acid were added to a solution of 430 mg (0.92 mmol) of N-(2-t-butyl-5-azidomethylphenyl)-3-(2,4-dimethoxyphenyl)octanamide [prepared as described in step (i) above] in 10 ml of acetone, and the resulting mixture was stirred for 1 hour. At the end of this time, the reaction mixture was filtered to remove zinc dust, and the filtrate was made alkaline by adding a saturated aqueous solution of sodium hydrogencarbonate. The mixture was then extracted with ethyl acetate. The extract was washed with water and then with a saturated aqueous solution of sodium chloride, after which it was dried over anhydrous magnesium sulfate. The solvent was removed by distillation under reduced pressure, and the resulting residue was purified by column chromatography through 50 g of silica gel using a 10:1 by volume mixture of ethyl acetate and methanol as the eluent, to give 354 mg (yield 86%) of the title compound as a foam-like substance.
Reaction SMILES: [CH2:1]=[CH:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:9][SiH:10]([CH3:14])[O:11][CH2:12][CH3:13]>[Pt].C1(C)C=CC=CC=1>[CH2:1]([Si:10]([CH3:14])([CH3:9])[O:11][CH2:12][CH3:13])[CH2:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1
Reactant: CCO[SiH](C)C
Reactant: C=Cc1ccccc1
Agent: [Pt]
Solvent: Cc1ccccc1
Product: CCO[Si](C)(C)CCc1ccccc1
Temperature: 41 °C
Yield: 27 %

Procedure:
Comparative Example 1. (Reaction between Styrene and Dimethylethoxysilane) A glass tube was filled with 312 mg of styrene and 312 mg of dimethylethoxysilane. The contents were combined with 1 μL of a toluene solution of a complex of divinylsiloxane and 0-valence platinum (platinum content: 0.4 Wt. %). The tube was sealed with Teflon tape and was heated for 30 minutes in an oil bath at 41° C. After cooling, the product was subjected to GC analysis. The analyses confirmed that the conversion of styrene was 36% and that phenethyldimethylethoxysilane was produced at a yield of 27%. The yield of (α-methylbenzyl)dimethylethoxysilane was 8.5%.
Reaction SMILES: Cl[C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@:15]([C:17]#[CH:18])([OH:16])[C@H:14]([OH:19])[C@@H:13]([CH2:20][OH:21])[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[NH3:22].O>>[NH2:22][C:2]1[C:3]2[CH:10]=[CH:9][N:8]([C@H:11]3[C@:15]([C:17]#[CH:18])([OH:16])[C@H:14]([OH:19])[C@@H:13]([CH2:20][OH:21])[O:12]3)[C:4]=2[N:5]=[CH:6][N:7]=1
Reactant: N
Reactant: C#C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1ccc2c(Cl)ncnc21
Solvent: O
Product: C#C[C@@]1(O)[C@H](O)[C@@H](CO)O[C@H]1n1ccc2c(N)ncnc21
Temperature: 100 °C

Procedure:
A mixture of (2R,3R,4R,5R)-2-(4-Chloro-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol (198.0 mg, 0.64 mmol,) and NH3.H2O (30 mL) in a glass pressure tube is heated at 100° C. for 5 h. The reaction mixture is concentrated to dry and purified by flash chromatography (CH2Cl2:MeOH=80:20) to yield (2R,3R,4R,5R)-2-(4-Amino-pyrrolo[2,3-d]pyrimidin-7-yl)-3-ethynyl-5-hydroxymethyl-tetrahydrofuran-3,4-diol as pale yellow solid. 1H NMR (300 MHz, MeOD): δ 8.07 (1H, s), 7.48 (1H, d, J=3.9 Hz), 6.58 (1H, d, J=3.6 Hz), 6.29 (1H, s), 4.49 (1H, d, J=8.4 Hz), 4.08-3.96 (2H, m), 3.90-3.75 (1H, m), 2.52 (1H, s). 1H NMR (300 MHz, DMSO-d6): δ 8.05 (1H, s), 7.41 (1H, d, J=3.6 Hz), 6.97 (2H, s), 6.55 (1H, d, J=3.6 Hz), 6.23 (1H, s), 6.16 (1H, s), 5.61 (1H, d, J=7.5 Hz), 5.13 (1H, t, J=4.9 Hz), 4.33 (1H, t, J=7.8 Hz), 3.90-3.70 (2H, m), 3.78-3.68 (1H, m), 3.01 (1H, s). 13C NMR (75 MHz, DMSO-d6): δ 157.4, 151.6, 150.1, 121.6, 102.4, 99.6, 89.6, 82.1, 81.8, 76.5, 75.8, 74.0, 59.7. ESI-MS: calcd. for C13H14N4O4 (290.1). found: 291.2.
Reaction SMILES: [C:1]1([S:7]([C:10]2[CH:18]=[C:17]3[C:13]([CH:14]=[CH:15][N:16]3[Si](C(C)C)(C(C)C)C(C)C)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].B(O)(O)O>C1COCC1.O>[C:1]1([S:7]([C:10]2[CH:18]=[C:17]3[C:13]([CH:14]=[CH:15][NH:16]3)=[CH:12][CH:11]=2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CC(C)[Si](C(C)C)(C(C)C)n1ccc2ccc(S(=O)(=O)c3ccccc3)cc21
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: OB(O)O
Agent: [F-]
Solvent: C1CCOC1
Solvent: O
Product: O=S(=O)(c1ccccc1)c1ccc2cc[nH]c2c1
Reaction time: 2 h
Yield: 92.7 %

Procedure:
To a solution of 6-phenylsulfonyl-1-triisopropylsilanyl-1H-indole 0.365 g, 0.88 mmol) in THF (10 mL) was added a solution of TBAF in THF (1 M, 1 mL) followed by a solution of boric acid (0.062 g, 1 mmol) in water (1 mL) and stirring was carried out for 2 h. The mixture was partitioned between water (50 mL) and DCM (3×30 mL) and the combined organic extracts were dried (Na2SO4) and evaporated in vacuo to give an oil. Chromatography (SiO2; gradient elution with 0-40% EtOAc in petrol) gave the title compound (0.21 g) as a colourless solid. MS: [M+H]+=258.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[CH:19][C:18]([O:21][CH2:22][C:23]([OH:25])=O)=[CH:17][CH:16]=2)=[CH:11][CH:10]=1.[NH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=1>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[F:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[N:20]=[CH:19][C:18]([O:21][CH2:22][C:23]([NH:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][N:28]=3)=[O:25])=[CH:17][CH:16]=2)=[CH:13][CH:14]=1
Reactant: O=C(O)COc1ccc(-c2ccc(F)cc2)nc1
Reactant: Nc1ccccn1
Solvent: O=C(O)C(F)(F)F
Product: O=C(COc1ccc(-c2ccc(F)cc2)nc1)Nc1ccccn1

Procedure:
The title compound was prepared analogously as described in Example 30(d) from 95 mg (0.26 mmol) of [6-(4-fluoro-phenyl)-pyridin-3-yloxy]-acetic acid trifluoroacetic acid salt and 39.5 mg (0.39 mmol) of 2-aminopyridine. Yield: 9.3 mg.