Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:13][CH2:12][O:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[Li]CCCC.[B:19](OC(C)C)([O:24]C(C)C)[O:20]C(C)C.[NH4+].[Cl-]>C1COCC1.CCOC(C)=O>[N:8]1([C:5]2[CH:6]=[CH:7][C:2]([B:19]([OH:24])[OH:20])=[CH:3][CH:4]=2)[CH2:13][CH2:12][O:11][CH2:10][CH2:9]1
Reactant: Brc1ccc(N2CCOCC2)cc1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: OB(O)c1ccc(N2CCOCC2)cc1
Reaction time: 8 h

Procedure:
To a solution of the compound prepared in step 1 (0.3 g) in THF (15 mL) was added n-BuLi (0.74 mL, 2 M in pentane) at 78° C. After 1 h triisopropyl borate (0.86 mL) was added at −78° C. The solution was warmed up slowly from −78° C. to room temperature and was stirred overnight. The solution was added to aqueous NH4Cl, a white precipitate formed, and EtOAc was added. The organic solution was separated, concentrated and co-evaporated with toluene. The residue washed twice with THF and filtered. The filtrate was concentrated and dried under high vacuum to give 0.25 g of light yellow precipitate. LC/MS m/z 208 (M+H)+.
Reaction SMILES: [CH2:1]([C:3]1[C:4]([CH:12]([S:15][CH2:16][C:17]([O:19]CC)=[O:18])[CH2:13][CH3:14])=[CH:5][C:6]2[O:10][CH2:9][O:8][C:7]=2[CH:11]=1)[CH3:2].[OH-].[Na+]>O.C(O)C>[CH2:1]([C:3]1[C:4]([CH:12]([S:15][CH2:16][C:17]([OH:19])=[O:18])[CH2:13][CH3:14])=[CH:5][C:6]2[O:10][CH2:9][O:8][C:7]=2[CH:11]=1)[CH3:2]
Reactant: CCOC(=O)CSC(CC)c1cc2c(cc1CC)OCO2
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: CCc1cc2c(cc1C(CC)SCC(=O)O)OCO2

Procedure:
4.0 g of ethyl [{1-(6-ethyl-1,3-benzodioxol-5-yl)propyl}thio]acetate and 2.6 g of sodium hydroxide were dissolved in a mixture comprising 20 ml of water and 20 ml of ethanol. The obtained solution was heated under reflux for 2 hours and distilled to remove the ethanol. The residue was washed with ether. The aqueous layer was acidified and extracted with chloroform. The extract was washed with water, dried over magnesium sulfate and concentrated in a vacuum. The residue was purified by silica gel column chromatography (ethyl acetate/hexane=2:8) to obtain 2.8 g of the title compunds as a colorless crystal.
Reaction SMILES: [CH:1]1([C:6]2[CH:7]=[C:8]([CH:12]=[C:13]([O:15][CH3:16])[N:14]=2)[C:9]([OH:11])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:17][C:18]1[CH:19]=[C:20]([CH:25]=[C:26]([CH3:37])[C:27]=1[O:28][CH2:29][C@@H:30]1[CH2:34][O:33]C(C)(C)[O:31]1)[C:21]([NH:23]O)=[NH:22]>>[Cl:17][C:18]1[CH:19]=[C:20]([C:21]2[N:23]=[C:9]([C:8]3[CH:12]=[C:13]([O:15][CH3:16])[N:14]=[C:6]([CH:1]4[CH2:2][CH2:3][CH2:4][CH2:5]4)[CH:7]=3)[O:11][N:22]=2)[CH:25]=[C:26]([CH3:37])[C:27]=1[O:28][CH2:29][C@@H:30]([OH:31])[CH2:34][OH:33]
Reactant: COc1cc(C(=O)O)cc(C2CCCC2)n1
Reactant: Cc1cc(C(=N)NO)cc(Cl)c1OC[C@@H]1COC(C)(C)O1
Product: COc1cc(-c2nc(-c3cc(C)c(OC[C@@H](O)CO)c(Cl)c3)no2)cc(C2CCCC2)n1

Procedure:
The title compound is prepared in analogy to Example 1 starting from 2-cyclopentyl-6-methoxy-isonicotinic acid and (R)-3-chloro-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-N-hydroxy-5-methyl-benzamidine; LC-MS**: tR=0.89 min, [M+H]+=460.18; 1H NMR (CDCl3): δ 1.72-1.80 (m, 2H), 1.84-1.95 (m, 4H), 2.03 (t br, J=5.8 Hz, 1H), 2.07-2.16 (m, 2H), 2.45 (s, 3H), 2.80 (d br, J=5.0 Hz, 1H), 3.20-3.29 (m, 1H), 3.83-3.93 (m, 2H), 4.02 (s, 3H), 4.11-4.14 (m, 2H), 4.15-4.21 (m, 1H), 7.30 (d, J=1.0 Hz, 1H), 7.50 (d, J=0.8 Hz, 1H), 7.95 (d, J=1.8 Hz, 1H), 8.09 (d, J=1.8 Hz, 1H).
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:14]1[C:18]2[N:19]=[CH:20][N:21]=[C:22]([NH2:23])[C:17]=2[C:16](I)=[CH:15]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[O:25]([C:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.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>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[CH2:13][N:14]1[C:18]2[N:19]=[CH:20][N:21]=[C:22]([NH2:23])[C:17]=2[C:16]([C:35]2[CH:36]=[CH:37][C:32]([O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)=[CH:33][CH:34]=2)=[CH:15]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)N1CCC[C@H]1Cn1cc(I)c2c(N)ncnc21
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: C1COCCO1
Product: CC(C)(C)OC(=O)N1CCC[C@H]1Cn1cc(-c2ccc(Oc3ccccc3)cc2)c2c(N)ncnc21
Yield: 91.1 %

Procedure:
A solution of (S)-2-(4-amino-5-iodo-pyrrolo[2,3-d]pyrimidin-7-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (500.00 mg, 1.13 mmol, 1.0 eq), 4-phenoxyphenyl-boronic acid (240.00 mg, 1.13 mmol, 1.0 eq), Pd(PPh3)4 (100.00 mg), and Na2CO3 (300.00 mg, 2.83 mmol, 2.5 eq) in Dioxane/H2O (40/10 ml) was stirred at 90° C. for 4 h. The reaction mixture was concentrated and purified by Pre-TLC to afford (S)-2-[4-amino-5-(4-phenoxy-phenyl)-pyrrolo[2,3-d]pyrimidin-7-ylmethyl]-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 91% in yield).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH:5]=[CH:6][CH:7]=1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].N1C=CN=C1>CN(C=O)C>[Si:16]([O:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH:5]=[CH:6][CH:7]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]
Reactant: CC(C)(C)OC(=O)Nc1cccc(O)c1
Reactant: CC(C)(C)[Si](C)(C)Cl
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)Nc1cccc(O[Si](C)(C)C(C)(C)C)c1

Procedure:
A solution of tert-butyl 3-hydroxyphenylcarbamate (12-2, 6.40 g, 30.6 mmol, 1 equiv), t-butyldimethylsilyl chloride (4.61 g, 30.6 mmol, 1.00 equiv), and imidazole (2.71 g, 39.8 mmol, 1.30 equiv) in DMF (50 mL) was stirred at 23° C. for 16 h. The reaction mixture was partitioned between half-saturated sodium bicarbonate solution and ethyl acetate (200 mL). The organic layer was washed successively with half-saturated ammonium chloride solution (100 mL), saturated sodium bicarbonate solution (100 mL), and brine (100 mL), then dried over sodium sulfate and concentrated to give tert-butyl 3-{[tert-butyl(dimethyl)silyl]oxy}phenylcarbamate (12-3) as a white solid. 1H NMR (400 MHz, CDCl3) δ 6.92 (t, 1H, J=7.8 Hz), 6.73 (m, 2H), 6.31 (ddd, 1H, J=7.8, 1.9, 0.7 Hz), 6.20 br s, 1H), 1.32 (s, 9H), 0.78 (s, 9H), −0.02 (s, 6H).
Reaction SMILES: [C:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH:16]=O)=[CH:8][CH:7]=1)(=[O:4])[CH:2]=[CH2:3].[Cl:18][C:19]1[CH:20]=[C:21]([CH:26]=[CH:27][C:28]=1[OH:29])[C:22]([NH:24][NH2:25])=[O:23]>>[C:1]([O:5][C:6]1[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[C:9]([CH:16]=[N:25][NH:24][C:22](=[O:23])[C:21]2[CH:26]=[CH:27][C:28]([OH:29])=[C:19]([Cl:18])[CH:20]=2)=[CH:8][CH:7]=1)(=[O:4])[CH:2]=[CH2:3]
Reactant: C=CC(=O)Oc1ccc(C=O)c2ccccc12
Reactant: NNC(=O)c1ccc(O)c(Cl)c1
Product: C=CC(=O)Oc1ccc(C=NNC(=O)c2ccc(O)c(Cl)c2)c2ccccc12

Procedure:
The compound was prepared according to the general procedure for the synthesis of alkylidene hydrazones from the condensation of 4-formyl-1-naphthyl acrylate (from step C) and 3-chloro-4-hydroxy benzoic acid hydrazide.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C@@:11]2([CH3:23])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12]2)[C:3]=1[CH2:24][CH2:25][OH:26].[CH3:27][S:28](Cl)(=[O:30])=[O:29]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[Cl:1][C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C@@:11]2([CH3:23])[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:21])([CH3:20])[CH3:22])=[O:17])[CH2:12]2)[C:3]=1[CH2:24][CH2:25][O:26][S:28]([CH3:27])(=[O:30])=[O:29]
Reactant: CS(=O)(=O)Cl
Reactant: CSc1nc(Cl)c(CCO)c(N[C@@]2(C)CCN(C(=O)OC(C)(C)C)C2)n1
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CSc1nc(Cl)c(CCOS(C)(=O)=O)c(N[C@@]2(C)CCN(C(=O)OC(C)(C)C)C2)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 113.7 %

Procedure:
To a solution of tert-butyl(3S)-3-{[6-chloro-5-(2-hydroxyethyl)-2-(methylsulfanyl)pyrimidin-4-yl]amino}-3-methylpyrrolidine-1-carboxylate (1.37 g, 3.40 mmol) in DCM (57 mL) was added TEA (1.66 mL, 11.9 mmol), methanesulfonylchloride (0.7 mL, 8.5 mmol) and DMAP (25 mg, 0.204 mmol) at 0° C. The mixture was stirred at 0° C. for 1 h and then at room temperature for 1 h. The reaction mixture was transferred to a separatory funnel with the aid of DCM. The solution was washed with water (3 times), dried over Na2SO4 and concentrated to give 1.86 g (>99%) of the title compound as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ 6.90 (d, J=18.5 Hz, 1 H), 4.28-4.19 (m, 2 H), 3.82-3.61 (m, 1 H), 3.60-3.42 (m, 1H), 3.41-3.36 (m, 1 H), 3.32-3.23 (m, 1 H), 3.13 (s, 3 H), 3.12-3.06 (m, 2 H), 2.45 (s, 3 H), 2.41-2.26 (m, 1 H), 2.07-1.97 (m, 1 H), 1.46 (d, J=11.4 Hz, 3 H), 1.38 (s, 9 H). m/z (APCI+) for C18H29ClN4O5S2 481.1 (M+H)+.
Reaction SMILES: C([O:3][C:4]([C:6]1[C:10]2[CH2:11][CH2:12][CH2:13][C:9]=2[N:8]([CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:7]=1)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[CH2:14]([N:8]1[C:9]2[CH2:13][CH2:12][CH2:11][C:10]=2[C:6]([CH2:4][OH:3])=[N:7]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1
Reactant: CCOC(=O)c1nn(Cc2ccccc2)c2c1CCC2
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1nn(Cc2ccccc2)c2c1CCC2
Yield: 1065.5 %

Procedure:
A solution of 1-benzyl-1,4,5,6-tetrahydro-3-cyclopentapyrazole carboxylic acid ethyl ester (6.0 g, 2.22 mmol) in THF (125 ml) was treated with lithium aluminum hydride (1.73 g, 44.4 mmol) and reacted at ambient temperature for 3.5 hours. Excess reagent was quenched with 10% aqueous THF (18 ml), 15% sodium hydroxide (5.4 ml) and water (5.4 ml). The mixture was diluted with ethyl acetate and filtered. The filtrate was washed with 5% brine solutions, dried, and evaporated to provide the title compound (5.40 g) as an oil.
Reaction SMILES: [CH2:1]([NH:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=1)[CH3:2].[H-].[Na+].[CH2:16]([O:23][C:24]1[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][C:25]=1[CH2:26]Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C>[CH2:16]([O:23][C:24]1[CH:31]=[CH:30][C:29]([Br:32])=[CH:28][C:25]=1[CH2:26][N:3]([C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][N:5]=1)[CH2:1][CH3:2])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1
Reactant: CCNc1ccc(C(=O)OC)cn1
Reactant: BrCc1cc(Br)ccc1OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCN(Cc1cc(Br)ccc1OCc1ccccc1)c1ccc(C(=O)OC)cn1
Temperature: 25 °C
Reaction time: 1 h
Yield: 71 %

Procedure:
A solution of methyl 6-ethylaminonicotinoate (152 g, 84.4 mmol) in DMF (50 ml) was cooled to 0° C. and treated with sodium hydride (60%. 75 mmol). The reaction was stirred for 1 hour and a solution of 2-benzyloxy-5-bromobenzylbromide (25 g, 70.2 mmol) in DMF (50 ml) added. The reaction was allowed to warm to ambient temperature and stirred for 18 hours. The reaction was quenched with water and extracted with ethyl acetate (three times). The organic layers were combined, washed with water and brine twice, dried (MgSO4) and evaporated to give a white solid. Recrystallisation from ethyl/acetate/hexane gave methyl 2-[N-(2-benzyloxy-5-bromobenzyl)-N-ethylamino]pyridine-5-carboxylate (22.7 g, 71%).
Reaction SMILES: [CH2:1]([O:8][CH2:9][CH2:10][CH2:11][CH:12]=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-].[CH3:15][NH2+]C.C=O>>[CH2:1]([O:8][CH2:9][CH2:10][C:11](=[CH2:15])[CH:12]=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=CCCCOCc1ccccc1
Reactant: C[NH2+]C
Agent: C=O
Agent: [Cl-]
Product: C=C(C=O)CCOCc1ccccc1
Reaction time: 1 h

Procedure:
8.0 g (44.9 mmol) of 4-benzyloxybutanal, 4.12 g (50.6 mmol) of dimethylammonium chloride and 3.95 ml (52.6 mmol) of 37% formaldehyde solution are kept at a bath temperature of 110° for one hour with stirring. The mixture is allowed to cool and is extracted three times with ether. The organic phases are washed with saturated sodium chloride solution, combined, dried over MgSO4, filtered and concentrated by evaporation. 4-benzyloxy-2-methylenebutanal is obtained in the form of a yellowish oil which can be reacted further without further purification.
Reaction SMILES: C(OC([N:8]1[CH2:13][CH2:12][CH:11]([S:14][C:15]2[C:20]3[C:21]4[CH:35]=[C:34]([C:36]5[CH:37]=[N:38][N:39]([CH3:41])[CH:40]=5)[CH:33]=[N:32][C:22]=4[N:23](COCC[Si](C)(C)C)[C:19]=3[CH:18]=[N:17][C:16]=2[C:42]#[N:43])[CH2:10][CH2:9]1)=O)(C)(C)C.FC(F)(F)C(O)=O>ClCCl>[CH3:41][N:39]1[CH:40]=[C:36]([C:34]2[CH:33]=[N:32][C:22]3[NH:23][C:19]4[CH:18]=[N:17][C:16]([C:42]#[N:43])=[C:15]([S:14][CH:11]5[CH2:12][CH2:13][NH:8][CH2:9][CH2:10]5)[C:20]=4[C:21]=3[CH:35]=2)[CH:37]=[N:38]1
Reactant: Cn1cc(-c2cnc3c(c2)c2c(SC4CCN(C(=O)OC(C)(C)C)CC4)c(C#N)ncc2n3COCC[Si](C)(C)C)cn1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cn1cc(-c2cnc3[nH]c4cnc(C#N)c(SC5CCNCC5)c4c3c2)cn1
Temperature: 25 °C
Reaction time: 22 h
Yield: 32.5 %

Procedure:
A mixture of 4-[6-cyano-3-(1-methyl-1H-pyrazol-4-yl)-9-(2-trimethylsilanyl-ethoxymethyl)-9H-dipyrido[2,3-b;4′,3′-d]pyrrol-5-ylsulfanyl]piperidine-1-carboxylic acid tert-butyl ester (106 mg, 0.17 mmol) and trifluoroacetic acid (1 mL) in dichloromethane (9 mL) was stirred at ambient temperature for 22 h. The reaction mixture was concentrated in vacuo and the resultant residue partitioned between dichloromethane (10 mL) and a saturated aqueous solution of sodium hydrogen carbonate (10 mL). The organic phase was concentrated in vacuo and the residue was adsorbed onto HM-N then purified by flash chromatography (silica, 25 g column, Si-SPE, 0-13% (2M ammonia in MeOH) in DCM) to afford the title compound as a pale yellow solid (21.5 mg, 25%). 1H NMR (DMSO-D6, 300 MHz): 9.04 (d, J=2.2 Hz, 1H), 9.02-8.97 (m, 2H), 8.29 (s, 1H), 7.98 (s, 1H), 3.93 (s, 3H), 3.54-3.21 (m, 1H), 2.97-2.86 (m, 2H), 2.49-2.36 (m, 2H), 1.89-1.77 (m, 2H), 1.65-1.47 (m, 2H). LCMS (Method F): RT=7.08 min, M+H+=390.
Reaction SMILES: [O:1]([CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][OH:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>ClCCl>[CH3:27][S:28]([O:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][O:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)(=[O:30])=[O:29]
Reactant: CS(=O)(=O)Cl
Reactant: OCCCCCCCCCCCOc1ccccc1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CS(=O)(=O)OCCCCCCCCCCCOc1ccccc1
Temperature: -8 °C
Reaction time: 0.5 h

Procedure:
To a solution of 10.6 g of 11-phenoxy-1-undecanol, 200 ml of dichloromethane and 8.4 ml of triethylamine chilled to -8° C. in an ice-salt bath is added dropwise over 10 minutes, a solution of 3.38 ml of methanesulfonyl chloride in 10 ml of dichloromethane. The solution is stirred for 30 minutes at -8° C., washed with 150 ml of ice-cold water, 75 ml of cold 10% hydrochloric acid, 75 ml of cold saturated sodium bicarbonate, 75 ml of cold saturated sodium chloride solution and dried over magnesium sulfate. The solvent is removed in vacuo to give off-white crystals, mp 54°-58° C.
Reaction SMILES: [N+:1]([C:4]1[CH:13]=[C:12]2[C:7]([CH2:8][CH2:9][NH:10][CH2:11]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].[CH:14]([O:17][C:18]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][C:19]=1[C:20](O)=[O:21])([CH3:16])[CH3:15]>>[CH:14]([O:17][C:18]1[CH:26]=[CH:25][C:24]([S:27]([CH3:30])(=[O:29])=[O:28])=[CH:23][C:19]=1[C:20]([N:10]1[CH2:9][CH2:8][C:7]2[C:12](=[CH:13][C:4]([N+:1]([O-:3])=[O:2])=[CH:5][CH:6]=2)[CH2:11]1)=[O:21])([CH3:16])[CH3:15]
Reactant: O=[N+]([O-])c1ccc2c(c1)CNCC2
Reactant: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)O
Product: CC(C)Oc1ccc(S(C)(=O)=O)cc1C(=O)N1CCc2ccc([N+](=O)[O-])cc2C1

Procedure:
Prepared in analogy to example 1.1 from 7-nitro-1,2,3,4-tetrahydro-isoquinoline (CA [42923-79-5]) and 2-isopropoxy-5-methanesulfonyl-benzoic acid (Example 2.1).
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[S:14][CH:13]=[N:12][CH:11]=2)[C:5]([C:15]#[N:16])=[C:4]([S:17][CH2:18][C:19]2[N:20]=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[S:22][CH:23]=2)[N:3]=1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[I:41]CCI>C1COCC1>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:10]2[S:14][C:13]([I:41])=[N:12][CH:11]=2)[C:5]([C:15]#[N:16])=[C:4]([S:17][CH2:18][C:19]2[N:20]=[C:21]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[S:22][CH:23]=2)[N:3]=1
Reactant: N#Cc1c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1-c1cncs1
Reactant: ICCI
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: N#Cc1c(N)nc(SCc2csc(-c3ccc(Cl)cc3)n2)c(C#N)c1-c1cnc(I)s1
Temperature: -78 °C
Reaction time: 1 h
Yield: 15 %

Procedure:
Under argon, 230 mg (0.493 mmol) of 2-amino-6-({[2-(4-chlorophenyl)-1,3-thiazol-4-yl]methyl}sulfanyl)-4-(1,3-thiazol-5-yl)pyridine-3,5-dicarbonitrile were dissolved in 15 ml of THF and cooled to −78° C. At this temperature, 1.182 ml (1.182 mmol) of lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1 M in THF) were added dropwise. After 1 h of stirring at −78° C., a solution of 0.143 ml (1.084 mmol) of 1,2-diiodethane in 5 ml of THF was added dropwise, and the reaction mixture was stirred at −78° C. for a further hour. The reaction was terminated by addition of 20 ml of 10% strength aqueous sodium thiosulfate solution. After the mixture had warmed to room temperature, the aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was purified by preparative HPLC (mobile phase A=water, B=acetonitrile; gradient: 0.0 min 10% B, 30 min 95% B, 34 min 95% B, 34.01 min 10% B, 38 min 10% B; flow rate: 50 ml/min; +0.1% TFA). The solid which had precipitated from the acetonitrile/water mixture was filtered off and dried under high vacuum. This gave 60 mg of the target compound in a purity of 76% (yield: 15% of theory).
Reaction SMILES: [CH3:1][N:2]([CH3:14])[CH:3]1[CH2:8][CH2:7][CH:6]([NH:9][C:10]([NH:12][CH3:13])=[S:11])[CH2:5][CH2:4]1.[CH3:15]I.O.[ClH:18]>CO.[Cl-]>[CH3:1][N:2]([CH3:14])[C@H:3]1[CH2:4][CH2:5][C@H:6]([NH:9][C:10](=[N:12][CH3:13])[S:11][CH3:15])[CH2:7][CH2:8]1.[ClH:18]
Reactant: CI
Reactant: CNC(=S)NC1CCC(N(C)C)CC1
Agent: Cl
Agent: [Cl-]
Solvent: O
Solvent: CO
Product: CN=C(N[C@H]1CC[C@H](N(C)C)CC1)SC
Temperature: 25 °C

Procedure:
A mixture of 0.50 g of 1-(4-dimethylaminocyclohexyl)-3-methyl-thiourea in 10 ml of MeOH, 1.16 ml of 2M HCl (in MeOH) and 0.36 g of methyliodide is stirred at RT. From the mixture obtained solvent is evaporated and the evaporation residue obtained is treated with H2O. 10 ml of a strong basic ion exchanger in chloride form (Amberlite IRA 400 (Cl)R) are added to the aqueous mixture obtained and the mixture obtained is stirred at RT. A precipitate obtained is filtrated off and the filtrate obtained is lyophilized. 1-(trans-4-Dimethylamino-cyclohexyl)-2,3-dimethyl-isothiourea in the form of a hydrochloride is obtained.
Reaction SMILES: [CH2:1]1[C:10]2[C:9]3[CH:11]=[CH:12][CH:13]=[CH:14][C:8]=3[CH2:7][CH2:6][C:5]=2[NH:4][C:3](=[O:15])[CH2:2]1.C([SiH](CC)CC)C.FC(F)(F)C(O)=O.C(=O)(O)[O-].[Na+]>ClCCl>[CH2:1]1[C@@H:10]2[C@H:5]([CH2:6][CH2:7][C:8]3[CH:14]=[CH:13][CH:12]=[CH:11][C:9]=32)[NH:4][C:3](=[O:15])[CH2:2]1
Reactant: O=C1CCC2=C(CCc3ccccc32)N1
Agent: CC[SiH](CC)CC
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: O=C1CC[C@H]2c3ccccc3CC[C@@H]2N1
Reaction time: 0.17 h
Yield: 78.7 %

Procedure:
A mixture of 1,4,5,6-tetrahydro-2H-benzo[f]quinolin-3-one (10 g, 50.2 mmol) and triethylsilane (17.5 g, 150 mmol) in dichloromethane (100 ml) was stirred for 10 minutes. Trifluoroacetic acid (69 g, 605 mmol) was added dropwise with stirring and the mixture was stirred for 8 hours at room temperature. The mixture was neutralized with saturated aqueous sodium bicarbonate and extracted with chloroform. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was washed with ethyl acetate, and dried to afford (4aRS,10bSR)-trans-1,4,4a,5,6,10b-hexahydro-2H-benzo[f]quinolin-3-one (7.94 g, 39.5 mmol, 79%) as white crystals.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6](F)[C:3]=1[CH:4]=[O:5].[C:11]1([OH:17])[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+].O>CC(N(C)C)=O>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([O:17][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[C:3]=1[CH:4]=[O:5]
Reactant: Oc1ccccc1
Reactant: O=Cc1c(F)cccc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(=O)N(C)C
Solvent: O
Product: O=Cc1c(Cl)cccc1Oc1ccccc1
Yield: 83.6 %

Procedure:
A mixture of 15.8 g (100 mmol) of 2-chloro-6-fluorobenzaldehyde, 9.4 g (100 mmol) of phenol and 20.7 g (150 mmol) of potassium carbonate in 150 ml of dimethylacetamide is heated under reflux for 4 hours The mixture is allowed to cool, water is added and the mixture is extracted 3× with tert-butyl methyl ether. The organic phases are washed with 2N sodium hydroxide solution and brine, dried over sodium sulfate and concentrated. Bulb tube distillation (175° C., 0.04 mbar) yields 19.46 g (83.64 mmol)=83.6% of 2-chloro-6-phenoxy-benzaldehyde in the form of a yellow oil, 1H-NMR (CDCl3, 200 MHz): 6.75-7.45 (m, 8H); 10.58 (s, 1H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH2:13]O)[N:10]=[CH:9]1.C1(P([N:40]=[N+:41]=[N-:42])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([N:15]2[CH2:19][C@H:18]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:17][C:16]2=[O:25])[CH:5]=[CH:6][C:7]=1[N:8]1[CH:12]=[C:11]([CH2:13][N:40]=[N+:41]=[N-:42])[N:10]=[CH:9]1
Reactant: [N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
Reactant: CC(=O)NC[C@H]1CN(c2ccc(-n3cnc(CO)c3)c(F)c2)C(=O)O1
Solvent: ClCCl
Solvent: C1CCC2=NCCCN2CC1
Product: CC(=O)NC[C@H]1CN(c2ccc(-n3cnc(CN=[N+]=[N-])c3)c(F)c2)C(=O)O1
Temperature: 25 °C
Reaction time: 48 h
Yield: 94.4 %

Procedure:
N-[(5 S)-3-(3-Fluoro-4-(4-hydroxymethylimidazol-1-yl)phenyl)-2-oxooxazolidin-5-yl-methyl]acetamide (1.74 g, 5 mM) was suspended in dry dichloromethane (60 ml), diphenylphosphoryl azide (2.47 g, 9 mM) and 1,8-diazabicyclo[5.4.0]undec-7-ene (1.82 g, 12 mM) added, and the mixture stirred under argon at ambient temperature for 48 hours. The resulting solution was columned on silica (75 g) through a sinter funnel, eluting with a gradient increasing in polarity from 0 to 10% methanol in dichloromethane. Relevant fractions were combined and evaporated to give the title product (1.76 g).
Reaction SMILES: C(=O)([O-])O.[Na+].[Cl:6][C:7]1[NH:8][CH:9]=[C:10]([N+:12]([O-:14])=[O:13])[N:11]=1.[CH2:15]([CH:17]1[O:19][CH2:18]1)[Cl:16]>C(#N)C>[Cl:6][C:7]1[N:8]([CH2:18][CH:17]([OH:19])[CH2:15][Cl:16])[CH:9]=[C:10]([N+:12]([O-:14])=[O:13])[N:11]=1
Reactant: ClCC1CO1
Reactant: O=[N+]([O-])c1c[nH]c(Cl)n1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC#N
Product: O=[N+]([O-])c1cn(CC(O)CCl)c(Cl)n1
Yield: 62.7 %

Procedure:
Sodium hydrogencarbonate (1.25 g, 14.91 mmol) was added to a solution of 2-chloro-4-nitro-1H-imidazole (2 g, 13.56 mmol) and epichlorohydrin (1.38 g, 14.91 mmol) in acetonitrile (60 ml), and the resulting mixture was stirred under reflux for 4 hours. The reaction mixture was allowed to return to room temperature, and concentrated under reduced pressure. To the residue, water (20 ml) was added, the resulting mixture was extracted with methylene chloride (15 ml) twice, and the extracts were dried over sodium sulfate, and then filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/n-hexane=1/1) to afford 2-chloro-1-(3-chloro-2-hydroxypropyl)-4-nitroimidazole (2.04 g, yield 63%) as a light yellow oil.