Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([NH2:16])=[N:14][CH:15]=2)[CH2:5][CH2:4]1.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[CH3:39][C:40]1[C:41]([C:45]2[C:54]3[N:53]=[CH:52][CH:51]=[N:50][C:49]=3[C:48]([C:55](O)=[O:56])=[CH:47][CH:46]=2)=[CH:42][S:43][CH:44]=1.CC1C(B(O)O)=CSC=1>C(Cl)Cl.CO>[CH3:2][N:3]1[CH2:8][CH2:7][N:6]([CH2:9][C:10]2[CH:11]=[CH:12][C:13]([NH:16][C:55]([C:48]3[C:49]4[N:50]=[CH:51][CH:52]=[N:53][C:54]=4[C:45]([C:41]4[C:40]([CH3:39])=[CH:44][S:43][CH:42]=4)=[CH:46][CH:47]=3)=[O:56])=[N:14][CH:15]=2)[CH2:5][CH2:4]1
Reactant: CN1CCN(Cc2ccc(N)nc2)CC1
Reactant: Cc1cscc1-c1ccc(C(=O)O)c2nccnc12
Agent: CN(C)C(On1nnc2ccccc21)=[N+](C)C
Agent: Cc1cscc1B(O)O
Agent: Cl
Solvent: CO
Solvent: ClCCl
Product: Cc1cscc1-c1ccc(C(=O)Nc2ccc(CN3CCN(C)CC3)cn2)c2nccnc12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
The title compound was prepared in analogy to the procedure described in Step 14.1 but stirring the reaction mixture at rt overnight, using 2 equiv of 5-(4-methyl-piperazin-1-ylmethyl)-pyridin-2-ylamine hydrochloride (Example 31), TBTU (2 equiv) and 8-(4-methyl-thiophen-3-yl)-quinoxaline-5-carboxylic acid. The carboxylic acid was synthesized as described in Steps 1.2-1.7 but using 4-methyl-3-thiopheneboronic acid in Step 1.4. Title compound: ESI-MS: 459.1 [M+H]+; tR=3.41 min (System 1); TLC: Rf=0.25 (DCM/MeOH, 9:1).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=2)[CH:5]=[CH:6][C:7]=1[CH:8]=[CH:9][O:10]C.Cl.CCOC(C)=O.CCCCCC>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:12]2[CH:17]=[CH:16][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:14][CH:13]=2)[CH:5]=[CH:6][C:7]=1[CH2:8][CH:9]=[O:10]
Reactant: COC=Cc1ccc(-c2ccc(C(F)(F)F)cc2)cc1F
Agent: Cl
Solvent: CCCCCC
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: O=CCc1ccc(-c2ccc(C(F)(F)F)cc2)cc1F
Temperature: 25 °C
Yield: 89.3 %

Procedure:
To a 0° C. solution of 3-fluoro-4-(2-methoxy-vinyl)-4′-trifluoromethyl-biphenyl (458 mg, 1.54 mmol) in THF (15 mL) is added dropwise concentrated hydrochloric acid (2.75 mL) and the reaction is warmed to room temperature. After 1 h TLC (30% EtOAc/hexane) indicates complete consumption of starting material. The reaction mixture was diluted with water and the pH is adjusted to 8 with solid NaHCO3. The reaction mixture is concentrated and the aqueous layer extracted with EtOAc (3×50 mL). The combined organic layers are washed with brine, dried (MgSO4), filtered, concentrated and chromatographed (40 g SiO2, 5% EtOAc/Hexanes) to yield the title compound (388 mg, 89%). 1NMR (400 MHz, CDCl3) δ ppm: 9.82 (s, 1H), 7.69 (q, 4H, J=8.4 Hz), 7.39 (dd, 1H, J=7.9, 1.3 Hz), 7.35 (dd, 1H, J=10.4, 1.5 Hz), 7.30 (t, 1H, J=7.7 Hz), 3.82 (s, 2H).
Reaction SMILES: [O:1]1[CH:6]2[C:7]([O:9][C:10](=[O:11])[CH:2]1[CH2:3][CH2:4][CH2:5]2)=O.[NH2:12][CH2:13][CH2:14][CH2:15][CH2:16][N:17]1[CH2:22][CH2:21][N:20]([C:23]2[CH:28]=[N:27][CH:26]=[C:25]([Cl:29])[N:24]=2)[CH2:19][CH2:18]1>C(Cl)Cl>[Cl:29][C:25]1[N:24]=[C:23]([N:20]2[CH2:19][CH2:18][N:17]([CH2:16][CH2:15][CH2:14][CH2:13][N:12]3[C:7](=[O:9])[CH:6]4[O:1][CH:2]([CH2:3][CH2:4][CH2:5]4)[C:10]3=[O:11])[CH2:22][CH2:21]2)[CH:28]=[N:27][CH:26]=1
Reactant: NCCCCN1CCN(c2cncc(Cl)n2)CC1
Reactant: O=C1OC(=O)C2CCCC1O2
Solvent: ClCCl
Product: O=C1C2CCCC(O2)C(=O)N1CCCCN1CCN(c2cncc(Cl)n2)CC1

Procedure:
Tetrahydropyran-2,6-dicarboxylic anhydride (3.12 g., 20 mmole) and 1-(4-aminobutyl)-4-(6-chloro-2-pyrazinyl)piperazine (5.94 g., 22 mmole) were combined in 200 ml. of methylene chloride and stirred for 30 minutes at room temperature. The solvent was removed in vacuum and replaced with 350 ml. of xylene. The mixture was refluxed for 50 hours with water removal via a Dean-Stark trap. The xylene was evaporated and the residue was filtered through 75 g. of silica gel with 2% ethanol/chloroform. The product was concentrated in vacuum and crystallized from isopropanol with the addition of 4N isopropanolic HCl. A second recrystallization from methanol gave 4.18 g. of the title compound as the monohydrochloride; m.p. 252°-253° C.
Reaction SMILES: Cl[CH2:2][C:3]1[N:4]=[CH:5][N:6]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[C:10](=[O:17])[N:9]([CH3:18])[CH2:8][C:7]=12.[OH-].[Na+]>[Pd]>[CH3:2][C:3]1[N:4]=[CH:5][N:6]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[C:10](=[O:17])[N:9]([CH3:18])[CH2:8][C:7]=12
Reactant: CN1Cc2c(CCl)ncn2-c2ccccc2C1=O
Agent: [Pd]
Agent: [Na+]
Agent: [OH-]
Product: Cc1ncn2c1CN(C)C(=O)c1ccccc1-2

Procedure:
1.30 g (5 mmol) of 3-(chloromethyl)-4,5-dihydro-5-methyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one and 200 mg (5 mmol) of sodium hydroxide are hydrogenated at room temperature and normal pressure in 20 ml of alcohol and in the presence of 100 mg of 10 percent palladium/carbon. The catalyst is removed, the solvent is evaporated and the residue is taken up in chloroform. The solution is washed with water, dried over magnesium sulphate and evaporated. There is obtained 4,5-dihydro-3,5-dimethyl-6H-imidazo[1,5-a][1,4]benzodiazepin-6-one of melting point 184.5°-185.5°.
Reaction SMILES: Br[CH2:2][C:3]1[C:8]([F:9])=[CH:7][C:6]([CH:10]([CH3:15])[C:11]([O:13]C)=[O:12])=[C:5]([F:16])[CH:4]=1.[O:17]=[C:18]1[CH2:22][CH2:21][CH2:20][CH:19]1C(OC)=O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[F:16][C:5]1[CH:4]=[C:3]([CH2:2][CH:19]2[CH2:20][CH2:21][CH2:22][C:18]2=[O:17])[C:8]([F:9])=[CH:7][C:6]=1[CH:10]([CH3:15])[C:11]([OH:13])=[O:12]
Reactant: COC(=O)C1CCCC1=O
Reactant: COC(=O)C(C)c1cc(F)c(CBr)cc1F
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CC(C(=O)O)c1cc(F)c(CC2CCCC2=O)cc1F
Yield: 75.6 %

Procedure:
Compound (32a) (4.8 g, 16.4 mmol), methyl 2-oxocyclo-pentanecarboxylate (2.5 mL, 21.9 mmol), and anhydrous potassium carbonate (4.0 g, 28.9 mmol) in acetone (200 mL) were allowed to react in the same manner as in Example 15. The obtained crude product was subjected to silica gel column chromatography and elution with an n-hexane/ethyl acetate (4:1) solution followed by conventional decarboxylation and hydrolysis to give 3.5 g (60%) of compound (33a) of interest as clear yellow oil.
Reaction SMILES: [NH2:1][C:2]1[C:9]([O:10][CH3:11])=[CH:8][CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[S].[CH2:13](N)[CH2:14][NH2:15]>>[NH:5]1[CH2:13][CH2:14][N:15]=[C:4]1[C:3]1[CH:6]=[CH:7][CH:8]=[C:9]([O:10][CH3:11])[C:2]=1[NH2:1]
Reactant: NCCN
Reactant: COc1cccc(C#N)c1N
Agent: [S]
Product: COc1cccc(C2=NCCN2)c1N
Temperature: 60 °C
Reaction time: 5 h
Yield: 50 %

Procedure:
2-Amino-3-methoxybenzonitrile (Step 2, 26.6 g, 179 mmol) was suspended in ethylenediamine (250 mL) and degassed thoroughly. To this was added sulfur powder (8 g, 251 mmol) slowly, then the reaction was heated to 60° C. and stirred 5 h. The reaction was then cooled, concentrated under reduced pressure, then treated with water (300 mL). The resulting suspension was collected by vacuum filtration and washed with water. The solid was purified via silica gel chromatography (50-100% EtOAc/hexanes). Fractions containing product were combined, the solvent removed under reduced pressure to give the title compound (17.3 g, 50%): HPLC MS RT=1.05 min, MH+=192.1; 1H NMR (DMSO-d6) δ: 3.81 (3H, s), 3.90 (4H, s), 6.65 (1H, t), 6.86 (1H, dd), 7.03 (1H, dd).
Reaction SMILES: [O:1]=[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][C:10]([CH:13]3[CH2:18][CH2:17][NH:16][CH2:15][CH2:14]3)=[C:9]([F:19])[CH:8]=2)[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3]1.N1C=CC=CC=1.[CH3:31][S:32](Cl)(=[O:34])=[O:33]>C(Cl)Cl>[CH3:31][S:32]([N:16]1[CH2:15][CH2:14][CH:13]([C:10]2[CH:11]=[CH:12][C:7]([N:6]3[CH2:5][C@H:4]([CH2:20][NH:21][C:22](=[O:24])[CH3:23])[O:3][C:2]3=[O:1])=[CH:8][C:9]=2[F:19])[CH2:18][CH2:17]1)(=[O:34])=[O:33]
Reactant: CC(=O)NC[C@H]1CN(c2ccc(C3CCNCC3)c(F)c2)C(=O)O1
Reactant: CS(=O)(=O)Cl
Solvent: ClCCl
Solvent: c1ccncc1
Product: CC(=O)NC[C@H]1CN(c2ccc(C3CCN(S(C)(=O)=O)CC3)c(F)c2)C(=O)O1
Temperature: 0 °C
Reaction time: 16 h

Procedure:
A solution of (S)-(−)-N-[[2-oxo-3-[4-(4-piperidinyl)-3-fluorophenyl]-5-oxazolidinyl]methyl]acetamide (EXAMPLE 20, 125 mg) and pyridine (60 μL) in dry methylene chloride (1.9 mL) at 0° C. is treated with methanesulfonyl chloride (32 μL), and the resulting mixture was stirred at 0° C. for one hour and at ambient temperature for 16 hours. The reaction mixture is then diluted with methylene chloride (30 μL), washed with water (10 mL) and saline (10 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure, and the residue is recrystallized from methylene chloride/diethyl ether to give the title compound, mp 240-242° C.
Reaction SMILES: [C:1]([C:3]1[CH:33]=[CH:32][CH:31]=[CH:30][C:4]=1[CH2:5][CH:6]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:10]2[CH:19]=[C:20]([O:25][CH3:26])[C:21]([O:23][CH3:24])=[CH:22][C:9]=2[N:8]([CH2:27][CH3:28])[C:7]1=[O:29])#[N:2]>[Ni].CO>[NH2:2][CH2:1][C:3]1[CH:33]=[CH:32][CH:31]=[CH:30][C:4]=1[CH2:5][CH:6]1[N:12]=[C:11]([C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:10]2[CH:19]=[C:20]([O:25][CH3:26])[C:21]([O:23][CH3:24])=[CH:22][C:9]=2[N:8]([CH2:27][CH3:28])[C:7]1=[O:29]
Reactant: CCN1C(=O)C(Cc2ccccc2C#N)N=C(c2ccccc2)c2cc(OC)c(OC)cc21
Agent: [Ni]
Solvent: CO
Product: CCN1C(=O)C(Cc2ccccc2CN)N=C(c2ccccc2)c2cc(OC)c(OC)cc21
Reaction time: 12 h
Yield: 70 %

Procedure:
Stir a mixture of 100 mg (0.23 mmol) of 3-(2-cyanobenzyl)-7,8-dimethoxy-1-ethyl-5-phenyl-1,3-dihydro-2H-1,4-benzodiazepin-2-one IIce, 10 mg of Raney nickel in 5 ml of MeOH under an H2 atmosphere at room temperature and pressure for 12 hours. Filter the suspension on celite, rinse three times with 10 ml of MeOH. Evaporate to dryness and purify by silica chromatography (AcOEt 5/CH2Cl2 4/EtOH 1, CH2Cl2 4/MeOH 1). Recrystallize in EtOH. Yield: 70%. M: 280° C. with degradation. 1H-NMR (CDCl3, 300 MHz): d 0.98–1.02 (m, 3H, CH3), 3.33–3.37 (m, 1H, 1H CHCH2), 3.54–3.59 (m, 5H, OCH3+1H NCH2CH3+1H CHCH2), 3.79–3.84 m, 1H, CHCH2), 3.89 (s, 3H, OCH3), 4.25–4.32 (m, 3H, CH2NH2+1H NCH2CH3), 6.40 (s, 1H Ar), 6.78 (s, 1H Ar), 7.02–7.63 (m, 10H Ar). Mass: (M+H)+=444.22
Reaction SMILES: [CH2:1]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N:13]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11].[OH:18]O>C(O)(=O)C>[CH2:1]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][N+:13]=1[O-:18])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH3:11]
Reactant: CCCCCCCCCCCc1ccccn1
Reactant: OO
Solvent: CC(=O)O
Product: CCCCCCCCCCCc1cccc[n+]1[O-]
Yield: 91 %

Procedure:
A solution of 11.0 g (47 mmol) of 2-n-undecylpyridine and 8 ml of an aqueous 35% hydrogen peroxide dissolved in 30 ml of glacial acetic acid was heated at 70° to 80° C. for 3 hours, and further 3 ml of the aqueous hydrogen peroxide was added, followed by heating at the same temperature for 9 hours. After cooling, the mixture was concentrated under a reduced pressure to about a half amount, and 50 ml of water was added and the mixture concentrated to a half amount (repeated twice). The concentrate was extracted with diethyl ether and washed with an aqueous sodium hydrogen carbonate solution. The product was dried over anhydrous sodium sulfate and concentrated under a reduced pressure. The residue was purified by separation by silica gel column chromatography (ethyl acetate→methanol:ethyl acetate=15:85) to give 10.7 g of the desired product (yield 91.0%).
Reaction SMILES: [NH:1]([C:8]([O:10][C:11]([CH3:14])([CH3:13])[CH3:12])=[O:9])[C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][SH:4].[OH-].[Na+].[CH3:17][CH:18]([SH:20])[CH3:19].II.Cl>O.C1COCC1.CCO>[C:11]([O:10][C:8]([NH:1][C@@H:2]([CH2:3][S:4][S:20][CH:18]([CH3:19])[CH3:17])[C:5]([OH:7])=[O:6])=[O:9])([CH3:14])([CH3:13])[CH3:12]
Reactant: CC(C)S
Reactant: CC(C)(C)OC(=O)N[C@@H](CS)C(=O)O
Agent: Cl
Agent: II
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Solvent: CCO
Product: CC(C)SSC[C@H](NC(=O)OC(C)(C)C)C(=O)O
Temperature: 25 °C
Reaction time: 24 h
Yield: 49.3 %

Procedure:
Boc-L-Cys-OH (221 mg, 1.0 mmol) was dissolved in H2O/THF (50% v/v, 20 mL). To the solution was added 10 N sodium hydroxide aq. (1.2 mL, 12 mmol) and 2-propane thiol (929 uL, 10 mmol) at 0° C. Then, a solution of iodine in 95% EtOH was added dropwise until the color of the reaction system changed from colorless to brown. The mixture was stirred for 1 d with warming to room temperature. After removing THF under reduced pressure, reaction mixture was neutralized by 1 N HCl aq. until pH 2-3. The solution was extracted with EtOAc. The extract was washed with saturated aq. NaS2O4 and brine, and dried over MgSO4. Concentration under reduced pressure followed by flash chromatography over silica gel in EtOAc/Hexanes/AcOH (75:25:1) gave Boc-L-Csp-OH (145.7 mg, 49% yield): 1H NMR (360 MHz, CDCl3) δ 5.34 (s, 1H), 4.59 (br, s, 1H), 3.24-3.14 (m, 2H), 3.09-3.00 (m, 1H), 1.47 (s, 9H), 1.32-1.30 (dd, 6H); LRMS (ESI) m/z calcd for C11H22NO4S2 (M+H)+ 296.1. found 296.1.
Reaction SMILES: [C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][CH:4]=1)#[CH:2].C([Li])CCC.CC(C)([O-])C.[K+].Br[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH2:40][CH2:41][CH3:42]>CCCCCC.O.O1CCCC1>[C:1]([C:3]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:6]=[CH:5][C:4]=1[CH2:42][CH2:41][CH2:40][CH2:39][CH2:38][CH2:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][CH3:25])#[CH:2]
Reactant: C#Cc1cccc2ccccc12
Reactant: CCCCCCCCCCCCCCCCCCBr
Agent: CC(C)(C)[O-]
Agent: [K+]
Agent: [Li]CCCC
Solvent: O
Solvent: CCCCCC
Solvent: C1CCOC1
Product: C#Cc1c(CCCCCCCCCCCCCCCCCC)ccc2ccccc12
Temperature: -90 °C
Reaction time: 1 h
Yield: 19.6 %

Procedure:
To 20 mL of a tetrahydrofuran solution of 2.88 g of ethynylnaphthalene was added 25 mL of a 1.6 mol/L hexane solution of n-butyl lithium at −50° C. under a nitrogen atmosphere, and the mixture was cooled to −90° C., and then 12 mL of a tetrahydrofuran solution of 2.3 g of potassium tert-butoxide was added thereto. After stirring at −80° C. for 1 hour, the temperature was raised up to 5° C. At −70° C., 6.90 g of bromooctadecane was dropped to the resulting solution, and stirred overnight at 30° C. 100 mL of water was dropped to the resulting solution at 0° C., and hexane was added thereto to extract the generated compound. The hexane layer was washed with 30 mL of distilled water for 3 times, dried over anhydrous magnesium sulfate for 24 hours, followed by filtration, and the solvent was removed by evaporation. The resulting product was purified on a column by using hexane as a developing solvent, thereby 1.5 g of 1-ethynyl-2-n-octadecylnaphthalene was obtained. The obtained 1-ethynyl-2-n-decylnaphthalene was analyzed by 1H-NMR (270 MHz, CDCl3), and the NMR spectra showed peak at δ 8.3 (1H), 7.8 (2H), 7.5 (3H), 3.6 (1H), 3.0 (2H) 1.7 (2H), 1.3 (32H), 0.9 (3H).
Reaction SMILES: Cl[C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:15])[CH:3]=1.[SH-:16].[Na+]>CO>[SH:16][C:2]1[C:11]([N+:12]([O-:14])=[O:13])=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:4]([CH3:15])[CH:3]=1
Reactant: COC(=O)c1cc([N+](=O)[O-])c(Cl)cc1C
Reactant: [SH-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1cc([N+](=O)[O-])c(S)cc1C
Reaction time: 2 h
Yield: 97.7 %

Procedure:
To a solution of methyl 4-chloro-2-methyl-5-nitrobenzoate (1.21 g) in methanol (20 ml) was added sodium hydrosulfide (561 mg), and the mixture was refluxed with stirring for 2 hours. After the reaction was complete, the reaction solution was concentrated, and methanol was concentrated under reduced pressure. Then, to the resultant were added water and 2N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered, concentrated under reduced pressure. The obtained residue was purified by column chromatography to give the title compound (1.17 g).
Reaction SMILES: C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[Cl:15][C:16]1[CH:17]=[C:18]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:19][NH:20][C:21]([NH:23][C:24]1[S:25][CH:26]=[C:27]([CH2:29][NH:30][CH3:31])[N:28]=1)=[O:22].[CH3:36][C:37]1[C:41]([CH:42]=O)=[C:40]([CH3:44])[O:39][N:38]=1.Cl.C([O-])(O)=O.[Na+]>C(Cl)Cl.CO>[Cl:15][C:16]1[CH:17]=[C:18]([CH:32]=[CH:33][C:34]=1[Cl:35])[CH2:19][NH:20][C:21]([NH:23][C:24]1[S:25][CH:26]=[C:27]([CH2:29][N:30]([CH2:42][C:41]2[C:37]([CH3:36])=[N:38][O:39][C:40]=2[CH3:44])[CH3:31])[N:28]=1)=[O:22]
Reactant: CNCc1csc(NC(=O)NCc2ccc(Cl)c(Cl)c2)n1
Reactant: Cc1noc(C)c1C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: O=C([O-])O
Solvent: ClCCl
Solvent: CO
Product: Cc1noc(C)c1CN(C)Cc1csc(NC(=O)NCc2ccc(Cl)c(Cl)c2)n1
Reaction time: 16 h

Procedure:
Sodium triacetoxyborohydride (86 mg, 0.4 mmol, 2.0 eq) was added to a dichloromethane (2 mL) solution of 1-(3,4-Dichloro-benzyl)-3-(4-methylaminomethyl-thiazol-2-yl)-urea (Example 132, 70 mg, 0.2 mmol) and 3,5-dimethylisoxazole-4-carbaldehyde (33 mg, 0.25 mmol, 1.25 eq). After 16 hours of stirring, methanol (1 mL) and aqueous HCl (0.5 mL, 1N) were added. The mixture was neutralized with dilute NaHCO3 solution. An aqueous work-up with dichloromethane and a chromatography (silica 0-3% MeOH in CH2Cl2) afforded the title compound. 1H NMR (400 MHz, CDCl3): 7.36 (m, 2H), 7.10 (dd, 1H), 6.64 (s, 1H), 4.32 (d, 2H), 3.46 (s, 3H), 3.21 (s, 3H), 2.28 (s, 3H), 2.16 (s, 3H), 2.07 (s, 3H). MS (ES+): M/Z 454 (M+1).
Reaction SMILES: B1(C)OC(C2C=CC=CC=2)(C2C=CC=CC=2)[C@H]2N1CCC2.B.[CH3:23][C:24]([O:27][C:28](=[O:39])[NH:29][CH2:30][CH2:31][C:32]([C:34]1[CH:38]=[CH:37][O:36][CH:35]=1)=[O:33])([CH3:26])[CH3:25]>O1CCCC1>[CH3:26][C:24]([O:27][C:28](=[O:39])[NH:29][CH2:30][CH2:31][C@H:32]([C:34]1[CH:38]=[CH:37][O:36][CH:35]=1)[OH:33])([CH3:23])[CH3:25]
Reactant: CC(C)(C)OC(=O)NCCC(=O)c1ccoc1
Agent: B
Agent: CB1OC(c2ccccc2)(c2ccccc2)[C@@H]2CCCN12
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)NCC[C@@H](O)c1ccoc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 83.5 %

Procedure:
(S)-2-Methyl-CBS-oxazaborolidine (1M in toluene, 0.84 ml, 0.836 mmol) was added to anhydrous tetrahydrofuran (50 ml) and the solution cooled to 0° C. Borane:tetrahydrofuran complex (1M, 5.02 ml, 5.02 mmol) was then added dropwise, keeping the temperature at 0° C. The mixture was stirred for 15 minutes then added the product of step (a) (2.0 g, 8.36 mmol) as a solution in tetrahydrofuran (50 ml), dropwise over 1 h keeping the temperature at 0° C. Stirred overnight whilst allowing to warm to room temperature. The reaction was quenched with methanol (5 ml) and stirred for a half hour. The solvent was removed in vacuo and another aliquot of methanol (20 ml) added. The solvent was removed in vacuo and the residue chromatographed on flash silica, eluting with hexane:ethyl acetate (1:1), to give the title compound as a colourless oil (1.685 g, 84%).
Reaction SMILES: [CH:1](=O)[C:2]1C=CC=CC=1.C1(S([C:18]2[CH:39]=[CH:38][CH:37]=[CH:36][C:19]=2[CH2:20][C:21]2[C:29]3[C:24](=[CH:25][CH:26]=[C:27]([F:30])[CH:28]=3)[N:23]([CH2:31][C:32]([OH:34])=[O:33])[C:22]=2[CH3:35])(=O)=O)CCCCC1>>[CH2:1]([O:34][C:32](=[O:33])[CH2:31][N:23]1[C:24]2[C:29](=[CH:28][C:27]([F:30])=[CH:26][CH:25]=2)[C:21]([CH2:20][C:19]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:18]=2)=[C:22]1[CH3:35])[CH3:2]
Reactant: Cc1c(Cc2ccccc2S(=O)(=O)C2CCCCC2)c2cc(F)ccc2n1CC(=O)O
Reactant: O=Cc1ccccc1
Product: CCOC(=O)Cn1c(C)c(Cc2ccccc2)c2cc(F)ccc21

Procedure:
Benzaldehyde was used as a starting material, otherwise this compound was prepared in a similar manner to Compound 1, using Procedure K.
Reaction SMILES: [CH2:1]([C:5]1[N:20]([CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH:29]([C:36]([O:38]CC)=[O:37])[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:24][CH:23]=2)[C:8]2=[N:9][C:10]([CH3:19])=[C:11]([NH:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:12]=[C:7]2[N:6]=1)[CH2:2][CH2:3][CH3:4].[OH-].[Na+]>C(O)C>[CH2:1]([C:5]1[N:20]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([O:28][CH:29]([C:36]([OH:38])=[O:37])[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)=[CH:26][CH:27]=2)[C:8]2=[N:9][C:10]([CH3:19])=[C:11]([NH:13][C:14]([N:16]([CH3:18])[CH3:17])=[O:15])[CH:12]=[C:7]2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2cc(NC(=O)N(C)C)c(C)nc2n1Cc1ccc(OC(C(=O)OCC)c2ccccc2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCCc1nc2cc(NC(=O)N(C)C)c(C)nc2n1Cc1ccc(OC(C(=O)O)c2ccccc2)cc1

Procedure:
Prepared analogously to Example 1b from 2-n-butyl-3-[4-[(α-ethoxycarbonyl)benzyloxy]benzyl]-5-methyl-6-dimethylaminocarbonylamino-imidazo[4,5-b]pyridine and 2N sodium hydroxide solution in ethanol.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([O:7][CH3:8])=[O:6].[Si:14](Cl)([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15].N1C=CN=C1.CN(C)C=O>CCCCCC>[Si:14]([O:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[C:5]([O:7][CH3:8])=[O:6])([C:17]([CH3:20])([CH3:19])[CH3:18])([CH3:16])[CH3:15]
Reactant: CC(C)(C)[Si](C)(C)Cl
Reactant: COC(=O)c1ccc(OC)c(O)c1
Agent: c1c[nH]cn1
Solvent: CN(C)C=O
Solvent: CCCCCC
Product: COC(=O)c1ccc(OC)c(O[Si](C)(C)C(C)(C)C)c1

Procedure:
A mixture of methyl 3-hydroxy-4-methoxybenzoate (120 mg, 0.66 mmol, prepared in Step 1, above), tert-butyldimethylsilyl chloride: (109 mg, 0.72 mmol), imidazole (98 mg, 1.24 mmol) and dimethylformamide (DMF, 2 ml) was stirred at room temperature over night. Extractive workup with hexane gave 90 mg of methyl 3-tert-butyldimethylsilyloxy-4-methoxybenzoate. NMR(δ): 0.18 (s, 3H), 1.00 (s, 9H),3.88 (s, 3H), 3.89 (s, 3 H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Cl:12])[N:8]=[C:7]([O:13][CH3:14])[C:6]([NH:15][C:16](=[O:20])OCC)=[N:5]2.[Cl:21][C:22]1[CH:23]=[C:24]([N:28]2[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]2)[CH:25]=[CH:26][CH:27]=1>>[Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[Cl:12])[N:8]=[C:7]([O:13][CH3:14])[C:6]([NH:15][C:16]([N:31]1[CH2:30][CH2:29][N:28]([C:24]3[CH:25]=[CH:26][CH:27]=[C:22]([Cl:21])[CH:23]=3)[CH2:33][CH2:32]1)=[O:20])=[N:5]2
Reactant: CCOC(=O)Nc1nc2cc(Cl)c(Cl)cc2nc1OC
Reactant: Clc1cccc(N2CCNCC2)c1
Product: COc1nc2cc(Cl)c(Cl)cc2nc1NC(=O)N1CCN(c2cccc(Cl)c2)CC1
Yield: 61 %

Procedure:
Ethyl N-(6,7-dichloro-2-methoxyquinoxalin-3-yl)carbamate and 1-(3-chlorophenyl)piperazine were reacted by the same way with the example 176 to obtain the titled compound (yield, 61%). 1H NMR (300 MHz, CDCl3) δ 3.31-3.30 (m, 4H), 3.75-3.76 (m, 4H), 4.15 (s, 3H), 6.80-6.82 (m, 1H), 6.90-6.91 (m, 2H), 7.18-7.23 (m, 1H), 7.32 (br s, 1H), 7.85 (s, 1H), 7.91 (s, 1H).