Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][O:2][C:3]([CH2:5][CH2:6][CH2:7][N:8]1[C:12](=[O:13])[CH:11]=[CH:10][S:9]1)=[O:4].S(Cl)([Cl:17])(=O)=O>>[Cl:17][C:10]1[S:9][N:8]([CH2:7][CH2:6][CH2:5][C:3]([O:2][CH3:1])=[O:4])[C:12](=[O:13])[CH:11]=1
Reactant: O=S(=O)(Cl)Cl
Reactant: COC(=O)CCCn1sccc1=O
Product: COC(=O)CCCn1sc(Cl)cc1=O
Temperature: 0 °C
Reaction time: 1 h

Procedure:
To prepare 2-(3-methoxycarbonylpropyl)-3-isothiazolone, Compound I (1.02 g, 2.5 mmol) was dissolved in25 ml distilled ethyl acetate and cooled to 0° C. Sulfuryl chloride (1.04 g, 7.75 mmol) was added slowly dropwise and the yellow solution stirred at 0° C. for 1 hr. During this time a white precipitate formed (5-chloro-2-(3-methoxycarbonylpropyl)-3-isothiazolone (200 mg)) which was removed by filtration. The resulting filtrate was concentrated and the residue flash-chromatographed (10% acetone-chloroform) to yield 2-(3-methoxycarbonylpropyl)-3-isothiazolone (120 mg) as a clear oil.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[N:15]=[C:14](/[N:16]=[C:17]2\[S:18][CH:19]=[CH:20][N:21]\2[CH2:22][O:23][CH3:24])[CH:13]=[CH:12][CH:11]=1)(C(C)(C)C)(C)C.FC(F)(F)C(O)=O>C(Cl)(Cl)Cl.CO>[CH3:24][O:23][CH2:22][N:21]1[CH:20]=[CH:19][S:18]/[C:17]/1=[N:16]\[C:14]1[N:15]=[C:10]([CH2:9][OH:8])[CH:11]=[CH:12][CH:13]=1
Reactant: COCn1ccs/c1=N\c1cccc(CO[Si](C)(C)C(C)(C)C)n1
Solvent: CO
Solvent: ClC(Cl)Cl
Solvent: O=C(O)C(F)(F)F
Product: COCn1ccs/c1=N\c1cccc(CO)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 14.28 g of 6-(((tert-butyl(dimethyl)silyl)oxy)methyl)-N-((2Z)-3-(methoxymethyl)-1,3-thiazol-2(3H)-ylidene)pyridin-2-amine in 30 ml of chloroform and 30 ml of methanol was added 30 ml of trifluoroacetic acid under cooling with ice, followed by stirring the reaction mixture at room temperature overnight. The reaction mixture was evaporated in vacuo. The resulting residue was neutralized with saturated aqueous sodium bicarbonate solution and extracted with ethyl acetate. The resulting ethyl acetate solution was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated in vacuo. The resulting residue was purified by a silica gel column chromatography (eluent: hexane to hexane/ethyl acetate =1/1) to give the title compound as a pale yellow solid.
Reaction SMILES: [C:1]1([CH:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8][C:9](O)=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.S(Cl)([Cl:20])=O>N1C=CC=CC=1>[C:1]1([CH:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH2:8][C:9]([Cl:20])=[O:10])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: O=C(O)CC(c1ccccc1)c1ccccc1
Reactant: O=S(Cl)Cl
Solvent: c1ccncc1
Product: O=C(Cl)CC(c1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
To a mixture of 3,3-diphenylpropionic acid (20 g, 88.4 mmol) and thionyl chloride (7.74 mL, 106.1 mmol) is added 5 drops of pyridine. The mixture is stirred at room temperature overnight (15 hours), and then distilled in vacuo to afford a light yellow oil, 17.88 g. The title compound forms as a light yellow solid when the oil is refrigerated overnight; mp 41°-43° C.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:20]4[CH:21]=[C:22]([O:25][CH2:26][CH:27]5[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]5)[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1.C=O.[C:35](O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>CO.ClCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C:8]2[N:9]=[C:10]([N:16]3[C:20]4[CH:21]=[C:22]([O:25][CH2:26][CH:27]5[CH2:28][CH2:29][N:30]([CH3:35])[CH2:31][CH2:32]5)[CH:23]=[CH:24][C:19]=4[N:18]=[CH:17]3)[S:11][C:12]=2[C:13]([NH2:15])=[O:14])[CH:5]=[CH:6][CH:7]=1
Reactant: CC(=O)O
Reactant: NC(=O)c1sc(-n2cnc3ccc(OCC4CCNCC4)cc32)nc1-c1cccc(Cl)c1
Agent: C=O
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: [Na+]
Solvent: ClCCl
Solvent: CO
Product: CN1CCC(COc2ccc3ncn(-c4nc(-c5cccc(Cl)c5)c(C(N)=O)s4)c3c2)CC1
Temperature: 25 °C
Reaction time: 18 h
Yield: 51.9 %

Procedure:
To a mixture of 0.030 g (0.06 mmole) of 4-(3-chloro-phenyl)-2-[6-(piperidin-4-ylmethoxy)-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.23), 0.0095 mL (0.13 mmole) of 37% aqueous formaldehyde solution, 0.0041 mL (0.070 mmole) of acetic acid and 2.1 mL of methanol-dichloromethane (2:5) was added 0.019 g (0.090 mmole) of sodium triacetoxyborohydride. The mixture was stirred at room temperature for 18 hours and then concentrated under reduced pressure. The residue was diluted with dichloromethane and ethyl acetate, washed with aqueous 1M sodium hydroxide solution and brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was recrystallized from methanol-dichloromethane to give 0.015 g of 4-(3-chloro-phenyl)-2-[6-(1-methyl-piperidin-4-ylmethoxy)-benzoimidazol-1-yl]-thiazole-5-carboxylic acid amide (I.24). MH+/Z=482
Reaction SMILES: [CH2:1]([O:8][C:9]([N:11]([CH3:16])[CH2:12][C:13]([O-:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN=C=NCCCN(C)C.[NH2:28][CH:29]1[CH2:32][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:30]1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH2:1]([O:8][C:9]([N:11]([CH3:16])[CH2:12][C:13]([NH:28][CH:29]1[CH2:30][N:31]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:32]1)=[O:15])=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CN(CC(=O)[O-])C(=O)OCc1ccccc1
Reactant: CC(C)(C)OC(=O)N1CC(N)C1
Agent: CCN=C=NCCCN(C)C
Agent: CN(C)c1ccncc1
Solvent: ClCCl
Product: CN(CC(=O)NC1CN(C(=O)OC(C)(C)C)C1)C(=O)OCc1ccccc1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of 2-(((benzyloxy)carbonyl)(methyl)amino)acetate (2.12 g, 9.50 mmol, prepared the previous step) and EDCI (1.99 g, 10.4 mmol) were stirred in anhydrous DCM (10 mL) for 15 minutes and then added to a solution of commercially available tert-butyl 3-aminoazetidine-1-carboxylate (1.64 g, 9.52 mmol) and DMAP (220 mg, 1.80 mmol) in DCM (90 mL). The reaction mixture was stirred at room temperature overnight and then concentrated in vacuo. The residue was dissolved in ethyl acetate, washed with saturated ammonium chloride solution, 1 N NaOH solution, brine and the organic layer dried over Na2SO4. After concentration in vacuo, the residue was purified by flash chromatography (silica gel, 0%-5% MeOH/EtOAc) to give a white solid after drying under high vacuum.
Reaction SMILES: [N+:1]([C:4]1[CH:25]=[CH:24][C:7]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[N:21]=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:6][CH:5]=1)([O-])=O.NN>C(O)C.[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:8]([N:10]2[C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][C:15]=3[CH2:14][N:13]3[N:21]=[CH:22][CH:23]=[C:12]3[CH2:11]2)=[O:9])=[CH:24][CH:25]=1
Reactant: O=C(c1ccc([N+](=O)[O-])cc1)N1Cc2ccnn2Cc2ccccc21
Agent: [Pd]
Agent: NN
Solvent: CCO
Product: Nc1ccc(C(=O)N2Cc3ccnn3Cc3ccccc32)cc1

Procedure:
To a solution of 5 mmol of 5,10-dihydro-5-(4-nitrobenzoyl)-4H-pyrazolo-[5,1-c][1,4]benzodiazepine in 25 ml of ethyl alcohol is added 0.3 g of 10% Pd/C and 15 mmol of hydrazine. The mixture is heated under reflux for 3 hours, and the mixture is filtered through diatomaceous earth. The filtrate is concentrated in vacuo to a residue which is dissolved in methylene chloride and passed through a thin pad of hydrous magnesium silicate. The filtrate is concentrated in vacuo to give the desired product which is purified by flash chromatography on silica gel to give the desired product as a solid, exact mass by mass spectrometry: 305.1402(M+H).
Reaction SMILES: [OH:1][C:2]1[C:3]([CH3:10])=[C:4]([CH:7]=[CH:8][CH:9]=1)[C:5]#[N:6].[Cl-].[Mg+2].[Cl-].[CH2:14]=[O:15].Cl>C1COCC1.C(N(CC)CC)C>[CH:14]([C:9]1[CH:8]=[CH:7][C:4]([C:5]#[N:6])=[C:3]([CH3:10])[C:2]=1[OH:1])=[O:15]
Reactant: Cc1c(O)cccc1C#N
Reactant: C=O
Agent: Cl
Agent: [Cl-]
Agent: [Mg+2]
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: Cc1c(C#N)ccc(C=O)c1O
Yield: 15.3 %

Procedure:
To a solution of 3-hydroxy-2-methylbenzonitrile (7.00 g) in THF (100 mL) were added triethylamine (13.1 g), magnesium chloride (12.4 g) and paraformaldehyde (6.60 g), and the mixture was heated with reflux for 16 hr under nitrogen atmosphere. The reaction mixture was poured into 1N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by flash silica gel column chromatography (ethyl acetate/petroleum ether) to give the title compound (1.30 g).
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]2[S:16][C:15]3[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:14]=3[C:13]=2[CH3:22])(=[O:11])=[O:10])=[C:4]([C:23]([F:26])([F:25])[F:24])[CH:3]=1.[CH3:27][O:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[CH:31][N:30]=1>COCCOC.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].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>[CH3:27][O:28][C:29]1[N:30]=[CH:31][C:32]([C:2]2[CH:7]=[CH:6][C:5]([NH:8][S:9]([C:12]3[S:16][C:15]4[CH:17]=[CH:18][C:19]([F:21])=[CH:20][C:14]=4[C:13]=3[CH3:22])(=[O:10])=[O:11])=[C:4]([C:23]([F:25])([F:26])[F:24])[CH:3]=2)=[CH:33][CH:34]=1
Reactant: Cc1c(S(=O)(=O)Nc2ccc(Br)cc2C(F)(F)F)sc2ccc(F)cc12
Reactant: COc1ccc(B(O)O)cn1
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: COCCOC
Solvent: CCO
Product: COc1ccc(-c2ccc(NS(=O)(=O)c3sc4ccc(F)cc4c3C)c(C(F)(F)F)c2)cn1
Yield: 76.4 %

Procedure:
This compound was prepared in analogy to Example 2 starting from 5-fluoro-3-methyl-benzo[b]thiophene-2-sulfonic acid(4-bromo-2-trifluoromethyl-phenyl)-amide (0.10 g) and 2-methoxy-5-pyridineboronic acid (0.065 g) in 1,2-dimethoxyethane (1.5 ml), ethanol (0.32 ml) and 2 M aqueous sodium carbonate solution (0.8 ml) with tetrakis(triphenylphosphine)palladium (0.012 g) to obtain the title compound (0.081 g) as a colorless solid. MS (ISP): 497.3 (M+H)+
Reaction SMILES: [Cl:1][C:2]1[CH:17]=[CH:16][C:5]([CH2:6][N:7]2[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH:9]=[CH:8]2)=[CH:4][CH:3]=1.[C:18](Cl)(=[O:22])[C:19](Cl)=[O:20].[NH2:24][C:25]1[CH:26]=[C:27]2[C:32](=[CH:33][CH:34]=1)[N:31]=[C:30]([CH3:35])[CH:29]=[CH:28]2>CCOCC.C1COCC1>[CH3:35][C:30]1[CH:29]=[CH:28][C:27]2[C:32](=[CH:33][CH:34]=[C:25]([NH:24][C:18](=[O:22])[C:19]([C:9]3[C:10]4[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=4)[N:7]([CH2:6][C:5]4[CH:4]=[CH:3][C:2]([Cl:1])=[CH:17][CH:16]=4)[CH:8]=3)=[O:20])[CH:26]=2)[N:31]=1
Reactant: Clc1ccc(Cn2ccc3ccccc32)cc1
Reactant: O=C(Cl)C(=O)Cl
Reactant: Cc1ccc2cc(N)ccc2n1
Solvent: CCOCC
Solvent: C1CCOC1
Product: Cc1ccc2cc(NC(=O)C(=O)c3cn(Cc4ccc(Cl)cc4)c4ccccc34)ccc2n1
Temperature: -4 °C
Reaction time: 8 h

Procedure:
At 0° C. and under nitrogen, a solution of 10.2 g (42.2 mmol) of 1-(4-chlorobenzyl)indole in 50 ml of ether is added dropwise to a solution of 5.50 ml of oxalyl chloride in 50 ml of ether. The mixture is heated at reflux for 2 hours and the solvent is then evaporated. 100 ml of tetrahydrofuran were then added to the residue and the solution was cooled to −4° C. and treated dropwise with a solution of 15.66 g (99.0 mmol) of 6-amino-2-methylquinoline in 350 ml of THF. The mixture is heated at reflux for 4 hours and allowed to stand at room temperature overnight. The 6-amino-2-methylquinoline hydrochloride is filtered off with suction, the precipitate is washed with THF, the filtrate is concentrated under reduced pressure and the residue is recrystallized from methyl ethyl ketone/methylene chloride.
Reaction SMILES: [C:1]([C:3]1[CH:4]=[C:5](B(O)O)[CH:6]=[CH:7][CH:8]=1)#[N:2].I[C:13]1[C:21]2[C:16](=[N:17][CH:18]=[N:19][C:20]=2[NH2:22])[N:15]([CH:23]([CH3:25])[CH3:24])[N:14]=1.C([O-])([O-])=O.[Na+].[Na+]>CCO.COCCOC.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>[NH2:22][C:20]1[N:19]=[CH:18][N:17]=[C:16]2[N:15]([CH:23]([CH3:25])[CH3:24])[N:14]=[C:13]([C:7]3[CH:8]=[C:3]([CH:4]=[CH:5][CH:6]=3)[C:1]#[N:2])[C:21]=12
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
Reactant: N#Cc1cccc(B(O)O)c1
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: CCO
Solvent: COCCOC
Product: CC(C)n1nc(-c2cccc(C#N)c2)c2c(N)ncnc21
Temperature: 80 °C
Yield: 41.2 %

Procedure:
A solution of 3-Cyanophenylboronic acid (23 mg, 0.15 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (40 mg, 0.13 mmol) in DME (12 ml). Pd(PPh3)4 (30 mg, 0.03 mmol) and saturated Na2CO3 (1.9 ml) were added and the reaction was heated to 80° C. under an argon atmosphere overnight. After cooling, the reaction was extracted with saturated NaCl and CH2Cl2. Organic phases were combined, concentrated in vacuo and purified by RP-HPLC (MeCN:H2O:0.1% TFA) to yield BA39 (14.9 mg, 41% yield). ESI-MS (M+H)+ m/z calcd 279.1, found 279.0.
Reaction SMILES: [OH:1][CH2:2][CH:3]1[CH2:7][O:6][C:5](=[O:8])[O:4]1.C(N(CC)CC)C.[C:16](Cl)(=[O:19])[CH:17]=[CH2:18]>C(Cl)(=O)C=C.C(N(CC)CC)C.C1C=CC=CC=1.O1CCOCC1>[C:16]([O:1][CH2:2][CH:3]1[CH2:7][O:6][C:5](=[O:8])[O:4]1)(=[O:19])[CH:17]=[CH2:18]
Reactant: C=CC(=O)Cl
Reactant: O=C1OCC(CO)O1
Solvent: C1COCCO1
Solvent: c1ccccc1
Solvent: CCN(CC)CC
Product: C=CC(=O)OCC1COC(=O)O1
Temperature: 0 °C

Procedure:
Following a similar preparation as described by D'Alelio and Huemmer (J. Poly. Sci., 5, 1967, pp. 307-321), to a two liter, three necked, round bottomed flask equipped with a paddle stirrer and thermometer, was added 87 g (0.74 mol.) of glycerol carbonate, followed by 1000 ml of benzene, 100 ml dioxane and 0.95 g of BHT. A drying tube and a nitrogen line were attached to the flask. Stirring was begun and the heterogeneous mixture was cooled to 0° C. with a brine bath. Two addition funnels were charged as follows: to the first was added 75 g (0.74 mol.) of triethylamine; to the second was added a solution of 100 ml of benzene and 60 g (0.66 mol.) of acryloyl chloride. Two drops of acryloyl chloride solution were added for every one drop of triethylamine. The addition took place over a period of two hours. The reaction contents were filtered through diatomaceous earth filtering media and the solution was washed with cold 5% HCl, followed by four 200 ml portions of water. 0.3 g of tert-butanol was added and the solution was dried over MgSO4. The solution was filtered to remove the drying agent and allowed to stand over a mixture of NaHCO3 and Na2SO4 for two days. The solution was filtered, transferred to a one liter, round bottomed flask and placed on a rotoevaporator. Without heat being applied, a vacuum of approximately 5 mmHg (667 Pa) was applied and the solvent was removed as completely as possible. 52 g (42%) of a light yellow liquid was recovered. 13C NMR identified the liquid to contain 86%, by weight, of the desired compound, the balance being benzene and dioxane.
Reaction SMILES: [Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]=O.[NH2:10][C:11]1[CH:15]=[CH:14][NH:13][N:12]=1.[C:16]([O:22][CH2:23][CH3:24])(=[O:21])[CH2:17][C:18]([CH3:20])=O>C(#N)C>[Cl:1][C:2]1[CH:9]=[CH:8][CH:7]=[CH:6][C:3]=1[CH:4]1[C:17]([C:16]([O:22][CH2:23][CH3:24])=[O:21])=[C:18]([CH3:20])[NH:10][C:11]2=[N:12][NH:13][CH:14]=[C:15]12
Reactant: Nc1cc[nH]n1
Reactant: O=Cc1ccccc1Cl
Reactant: CCOC(=O)CC(C)=O
Solvent: CC#N
Product: CCOC(=O)C1=C(C)Nc2n[nH]cc2C1c1ccccc1Cl
Temperature: 25 °C
Yield: 22.2 %

Procedure:
A solution of 2-chlorobenzaldehyde (1.7 g), 3-aminopyrazole (1.0 g) and ethyl acetoacetate (1.6 g) in acetonitrile (20 mL) was heated under reflux overnight. The reaction mixture was cooled to room temperature and the solvent was evaporated under reduced pressure to give an oil. The oil was purified by silica gel column chromatography (eluent:hexane-ethyl acetate (8:2)) to give the title compound (850 mg) as colorless crystals.
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8](S(C)(=O)=O)[C:5]2=[N:6][CH:7]=1.[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1.CN([CH:23]=[O:24])C>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:15]1([C:23]([C:2]2[CH:3]=[C:4]3[CH:10]=[CH:9][NH:8][C:5]3=[N:6][CH:7]=2)=[O:24])[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: C1CCNC1
Reactant: CS(=O)(=O)n1ccc2cc(Br)cnc21
Reactant: CN(C)C=O
Agent: Cl[Pd]Cl
Agent: [Fe+2]
Agent: c1ccc(P(c2ccccc2)[c-]2cccc2)cc1
Product: O=C(c1cnc2[nH]ccc2c1)N1CCCC1
Temperature: 80 °C
Yield: 34 %

Procedure:
A mixture of 5-bromo-1-methanesulfonyl-1H-pyrrolo[2,3-b]pyridine (300 mg, 1.1 mmol), PdCl2(dppf) (55 mg, 0.07 mmol), and pyrrolidine (2 mL) in DMF (5 mL) was charged with CO balloon. The system was degassed with vacuum twice before it was heated to 80° C. for 6 h. The solution was cooled and poured into water. The aqueous solution was extracted with ethyl acetate (3×50 mL), the combined organic layers were dried over Na2SO4, and the solvent was removed by vacuum evaporation. The crude product was treated with 6N NaOH in MeOH for 2 h. MeOH was removed by evaporation. The aqueous solution was neutralized with 6N HCl to pH 8 and extracted with ethyl acetate. The combined organic layers were dried over Na2SO4 and the solvent was removed by vacuum evaporation to give a yellow solid (80 mg, 0.37 mmol, 34%), which was used directly for the next step. MS (ES+): m/e=216.1 (M+H); LC: 2.18 min.
Reaction SMILES: [CH2:1]1[O:3][CH2:2]1.[CH2:4]([C:8]#[CH:9])[CH2:5][CH2:6][CH3:7]>>[CH2:1]([OH:3])[CH2:2][C:7]#[C:6][CH2:5][CH2:4][CH2:8][CH3:9]
Reactant: C1CO1
Reactant: C#CCCCC
Product: CCCCC#CCCO

Procedure:
Into the solution of the Grignard reagent obtained above and kept at 0° to 60° C., ethylene oxide is added dropwise preferably in an amount of 1.6 to 3 times by moles based on the starting butylacetylene and the reaction mixture is hydrolyzed by contacting with an aqueous acidic solution followed by distillation to give 3-octyn-1-ol (reaction (ii)). The yield is usually 80 to 85% of the theoretical value.
Reaction SMILES: [OH:1][CH:2]([C:5]1[CH:6]=[C:7]([Si:10]([CH2:15][CH3:16])([CH2:13][CH3:14])[CH2:11][CH3:12])[O:8][CH:9]=1)[CH2:3][OH:4].C([Si](CC)(CC)C1OC=C(C=O)C=1)C.C[Si](C1C=COC=1C=O)(C)C.[C:42](Cl)(=[O:54])[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53]>C(N(CC)CC)C>[OH:1][CH:2]([C:5]1[CH:6]=[C:7]([Si:10]([CH2:13][CH3:14])([CH2:11][CH3:12])[CH2:15][CH3:16])[O:8][CH:9]=1)[CH2:3][O:4][C:42](=[O:54])[CH2:43][CH2:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH2:52][CH3:53]
Reactant: CCCCCCCCCCCC(=O)Cl
Reactant: CC[Si](CC)(CC)c1cc(C(O)CO)co1
Agent: CC[Si](CC)(CC)c1cc(C=O)co1
Agent: C[Si](C)(C)c1ccoc1C=O
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCC(=O)OCC(O)c1coc([Si](CC)(CC)CC)c1

Procedure:
4-(1,2-Dihydroxyethyl)-2-triethylsilylfuran (prepared substantially as described above using 5-triethylsilyl-3-furaldehyde in place of the corresponding trimethylsilyl furaldehyde) is reacted with dodecanoyl chloride in the presence of triethylamine to give 4-(1-hydroxy-2-dodecanoyloxyethyl)-2-triethylsilylfuran. Treating this 1-hydroxy compound with acetic anhydride and pyridine gives 4-(1-acetoxy-2-dodecanoyl-oxyethyl)-2-triethylsilylfuran.
Reaction SMILES: [C:1](N1C=CN=C1)([N:3]1C=CN=[CH:4]1)=O.[F:13][C:14]([F:30])([F:29])[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][C:16]=1[C:21]1[O:25][N:24]=[C:23]([C:26]([OH:28])=O)[N:22]=1.CNC>O1CCCC1>[CH3:1][N:3]([CH3:4])[C:26]([C:23]1[N:22]=[C:21]([C:16]2[CH:17]=[N:18][CH:19]=[CH:20][C:15]=2[C:14]([F:13])([F:30])[F:29])[O:25][N:24]=1)=[O:28]
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: O=C(O)c1noc(-c2cnccc2C(F)(F)F)n1
Agent: CNC
Solvent: C1CCOC1
Product: CN(C)C(=O)c1noc(-c2cnccc2C(F)(F)F)n1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
5.8 g of carbonyldiimidazole are initially charged in 90 ml of tetrahydrofuran and, a little at a time, admixed with 9 g of 5-(4-trifluoromethyl-3-pyridyl)-1,2,4-oxadiazole-3-carboxylic acid. The mixture is stirred at room temperature for 15 min and then heated at 50° C. for 2 h. After cooling to room temperature, 2.3 g of dimethylamine are introduced in a very gentle gas stream over a period of 2 h. After a reaction time of 12 h, the mixture is concentrated and taken up in 200 ml of diethyl ether. The mixture is washed with ice-cold half conc. hydrochloric acid solution, washed neutral with sat. sodium bicarbonate sol., dried over magnesium sulfate and concentrated under reduced pressure. This gives a slightly yellow oil which solidifies after a number of days to a solid of mp. 52-54° C.
Reaction SMILES: [CH2:1]([NH:5][CH2:6][C:7]1[S:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:13]=2)=[CH:10][CH:11]=1)[CH:2]([CH3:4])[CH3:3].C/C(/C)=C(/OC)\O[Si](C)(C)C.[CH2:33]([S:37](Cl)(=[O:39])=[O:38])[CH2:34][CH2:35][CH3:36]>ClCCl>[CH2:1]([N:5]([CH2:6][C:7]1[S:8][C:9]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([S:18]([CH3:21])(=[O:20])=[O:19])[CH:13]=2)=[CH:10][CH:11]=1)[S:37]([CH2:33][CH2:34][CH2:35][CH3:36])(=[O:39])=[O:38])[CH:2]([CH3:4])[CH3:3]
Reactant: CCCCS(=O)(=O)Cl
Reactant: CC(C)CNCc1ccc(-c2cccc(S(C)(=O)=O)c2)s1
Agent: COC(O[Si](C)(C)C)=C(C)C
Solvent: ClCCl
Product: CCCCS(=O)(=O)N(Cc1ccc(-c2cccc(S(C)(=O)=O)c2)s1)CC(C)C
Temperature: 25 °C
Reaction time: 48 h

Procedure:
To a stirred solution of isobutyl-[5-(3-methanesulfonyl-phenyl)-thiophen-2-ylmethyl]-amine (example 15, step 2, 56 mg) in dichloromethane (1 mL) were added dimethylketene methyltrimethylsilylacetal (60 mg) and 1-butanesulfonyl chloride (41 mg). The mixture was stirred for 2 days at r.t. The mixture was diluted with dichloromethane and washed with water. The organic phase was dried (MgSO4), filtered and concentrated under reduced pressure. The product was purified by chromatography (SiO2, cyclohexane/ethyl acetate 9:1 to 1:1) to give butane-1-sulfonic acid isobutyl-[5-(3-methanesulfonyl-phenyl)-thiophen-2-ylmethyl]-amide as a colorless solid. MS: 461.4 ([M+NH4]+)
Reaction SMILES: ClC(OC(Cl)C)=O.C([N:15]1[CH2:20][CH2:19][N:18]([C@@H:21]2[CH2:25][CH2:24][N:23]([C:26](=[O:56])[CH:27]([N:34]3[C:38]4[CH:39]=[C:40]([Cl:43])[CH:41]=[CH:42][C:37]=4[N:36]([S:44]([C:47]4[CH:52]=[CH:51][C:50]([O:53][CH3:54])=[CH:49][CH:48]=4)(=[O:46])=[O:45])[C:35]3=[O:55])[C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:22]2)[CH2:17][CH2:16]1)C1C=CC=CC=1>ClCCl>[Cl:43][C:40]1[CH:41]=[CH:42][C:37]2[N:36]([S:44]([C:47]3[CH:48]=[CH:49][C:50]([O:53][CH3:54])=[CH:51][CH:52]=3)(=[O:46])=[O:45])[C:35](=[O:55])[N:34]([CH:27]([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[C:26](=[O:56])[N:23]3[CH2:24][CH2:25][C@@H:21]([N:18]4[CH2:17][CH2:16][NH:15][CH2:20][CH2:19]4)[CH2:22]3)[C:38]=2[CH:39]=1
Reactant: COc1ccc(S(=O)(=O)n2c(=O)n(C(C(=O)N3CC[C@@H](N4CCN(Cc5ccccc5)CC4)C3)c3ccccc3)c3cc(Cl)ccc32)cc1
Agent: CC(Cl)OC(=O)Cl
Solvent: ClCCl
Product: COc1ccc(S(=O)(=O)n2c(=O)n(C(C(=O)N3CC[C@@H](N4CCNCC4)C3)c3ccccc3)c3cc(Cl)ccc32)cc1
Temperature: 0 °C

Procedure:
118 mg (0.82 mmol) of 1-chloroethyl chloroformate were added to a solution of 550 mg (0.79 mmol) of 3-{2-[(R)-3-(4-benzylpiperazin-1-yl)-pyrrolidin-1-yl]-2-oxo-1-phenylethyl}-5-chloro-1-(4-methoxybenzenesulfonyl)-1,3-dihydrobenzimidazol-2-one (Example 142) in 5 ml dry dichloromethane while stirring at 0° C. The reaction mixture was subsequently stirred at 0° C. for 1 h and then at room temperature overnight. The solvent was removed in vacuo, and the residue was dissolved in 20 ml of methanol.