Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[CH:22]([C:25]1[CH:31]=[CH:30][CH:29]=[C:28]([CH:32]([CH3:34])[CH3:33])[C:26]=1[NH2:27])([CH3:24])[CH3:23].[Br:35][CH2:36][CH2:37][CH2:38][C:39](O)=[O:40]>CN(C=O)C>[Br:35][CH2:36][CH2:37][CH2:38][C:39]([NH:27][C:26]1[C:25]([CH:22]([CH3:24])[CH3:23])=[CH:31][CH:30]=[CH:29][C:28]=1[CH:32]([CH3:34])[CH3:33])=[O:40]
Reactant: O=C(O)CCCBr
Reactant: CC(C)c1cccc(C(C)C)c1N
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(C)c1cccc(C(C)C)c1NC(=O)CCCBr
Temperature: 25 °C
Reaction time: 12 h
Yield: 31.9 %

Procedure:
WSC (2.3 g, 12 mmols) and HOBt (1.49 g, 15 mmols) were added to a DMF (30 ml) solution of 2,6-diisoproylaniline (1.97 g, 10 mmols) and 4-bromobutyric acid (2.71 g, 15 mmols), and stirred at room temperature for 12 hours. The reaction mixture was extracted with ether. The organic layer was washed with water, 1 N HCl, an aqueous saturated solution of sodium hydrogencarbonate and saturated saline in that order, and dried with anhydrous magnesium sulfate, and the solvent was evaporated. Then, the residue was purified through silica gel column chromatography (developer: hexane/acetone=5/1), and the resulting crystals were recrystallized from ether-hexane to obtain 1.04 g (32%) of 4-bromo-N-(2,6-diisopropylphenyl)butanamide as colorless needle-like crystals.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1.[F:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15]([C:20](O)=[O:21])=[CH:14]2.ON1C2C=CC=CC=2N=N1.N=C=N.C(=O)([O-])[O-].[N-]=C=O>CN(C=O)C>[F:10][C:11]1[CH:12]=[C:13]2[C:17](=[CH:18][CH:19]=1)[NH:16][C:15]([C:20]([N:1]1[CH2:6][CH2:5][CH:4]([CH2:7][CH2:8][OH:9])[CH2:3][CH2:2]1)=[O:21])=[CH:14]2
Reactant: O=C(O)c1cc2cc(F)ccc2[nH]1
Reactant: OCCC1CCNCC1
Agent: N=C=N
Agent: O=C([O-])[O-]
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: O=C(c1cc2cc(F)ccc2[nH]1)N1CCC(CCO)CC1
Reaction time: 8 h
Yield: 102.5 %

Procedure:
To a solution of 4.1 mg of 4-piperidine ethanol, 5.3 mg of 5-fluoro-1H-indole-2-carboxylic acid, and 4.0 mg of 1-hydroxybenzotriazole in 0.6 mL of DMF was added 100 mg of PS-Carbodiimide (Argonaut Technologies) at room temperature, followed by stirring overnight. To the reaction liquid were added 50 mg of MP-Carbonate (Argonaut Technologies) and 50 mg of PS-Isocyanate (Argonaut Technologies) at room temperature, followed by stirring for 2 hours, and insoluble material was filtered. The filtrate was concentrated under reduced pressure to obtain 8.8 mg of 2-{1-[(5-fluoro-1H-indol-2-yl)carbonyl]piperidin-4-yl}ethanol.
Reaction SMILES: [CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3]1.CN(C)[C:13](=[O:17])[CH2:14][CH2:15][CH3:16].O=P(Cl)(Cl)Cl>C(Cl)(Cl)Cl>[CH3:1][N:2]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([C:13](=[O:17])[CH2:14][CH2:15][CH3:16])=[CH:3]1
Reactant: CCCC(=O)N(C)C
Reactant: Cn1ccc2ccccc21
Solvent: ClC(Cl)Cl
Solvent: O=P(Cl)(Cl)Cl
Product: CCCC(=O)c1cn(C)c2ccccc12
Reaction time: 2 h
Yield: 72 %

Procedure:
To a solution of 1-methyl-1H-indole (5.9 g, 45.0 mmol) in CHCl3 (150 mL) was added N,N-dimethylbutyramide (5.8 g, 50.4 mmol, 1.1 eq) followed by POCl3 (5.0 mL, 53.5 mmol, 1.2 eq) at 0° C. Then mixture was heated to reflux and stirred for 2 h. The reaction was quenched with saturated aqueous NaHCO3 then stirred for 30 min at room temperature. The mixture was extracted by CH2Cl2 (3×40 mL) and combined organic layers were dried over Na2SO4. The crude product was purified by flash column chromatography (0-50% EtOAc in hexanes) to afford 1-(1-methyl-1H-indol-3-yl)butan-1-one (6.53 g, 32.4 mmol, 72%).
Reaction SMILES: F[C:2]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[CH:6][C:3]=1[C:4]#[N:5].[CH3:12][S-:13].[Na+].O>CN(C)C=O>[CH3:11][O:10][C:7]1[CH:8]=[CH:9][C:2]([S:13][CH3:12])=[C:3]([CH:6]=1)[C:4]#[N:5]
Reactant: COc1ccc(F)c(C#N)c1
Reactant: C[S-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: COc1ccc(SC)c(C#N)c1
Yield: 70 %

Procedure:
(Step 1) A mixture of 2-fluoro-5-methoxybenzonitrile (10 g) and sodium methanethiolate (5.1 g) was stirred in N,N-dimethylformamide (20 ml) at 60° C. for 3 hr. The reaction solution was treated with water, and extracted with ethyl acetate. The extract was washed successively with 1N hydrochloric acid, aqueous sodium hydrogen carbonate solution and saturated brine, and dried over magnesium sulfate. The solvent was evaporated under reduced pressure. The obtained residue was crystallized from ethyl acetate-hexane to give 5-methoxy-2-(methylsulfanyl)benzonitrile (8.3 g).
Reaction SMILES: COC(OC)[N:4]1[CH:8]=[CH:7][CH:6]=[N:5]1.C([Li])CCC.[Cl:16][C:17]1[CH:31]=[CH:30][C:20]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)=[O:22])=[CH:19][CH:18]=1.O>O1CCCC1.CCCCCC>[Cl:16][C:17]1[CH:31]=[CH:30][C:20]([C:21]([C:23]2[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=2)([C:8]2[CH:7]=[CH:6][NH:5][N:4]=2)[OH:22])=[CH:19][CH:18]=1
Reactant: O=C(c1ccc(Cl)cc1)c1ccc(Cl)cc1
Reactant: COC(OC)n1cccn1
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Solvent: CCCCCC
Product: OC(c1ccc(Cl)cc1)(c1ccc(Cl)cc1)c1cc[nH]n1
Reaction time: 48 h
Yield: 29.8 %

Procedure:
A solution of 14.2 g of 1-(dimethoxymethyl)-pyrazole in 125 ml of tetrahydrofuran at -40° C. was treated with 79 ml of a 1.27M solution of n-butyllithium in hexane under a nitrogen atmosphere. When this addition was complete, 25.2 g of 4,4'-dichlorobenzophenone were added. The reaction was stirred for 48 hours allowing the temperature to come to room temperature. The reaction mixture was added to 200 ml of water and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate, filtered and evaporated. The semi-solid residue was triturated with toluene. The toluene filtrate was collected and evaporated and the residue therefrom was purified by high pressure liquid chromatography over silica gel. The appropriate fractions were combined and evaporated to provide 9.5 g of the desired title product. Crystallization from 15% ethyl acetate in hexane provided material with a melting point of 138°-140° C. A second recrystallization provided material with the following analysis.
Reaction SMILES: C([C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1)=O.[CH:13]([O:18][CH3:19])([O:16][CH3:17])OC>CO.S(=O)(=O)(O)O.C(Cl)Cl>[CH3:19][O:18][CH:13]([O:16][CH3:17])[C:3]1[CH:12]=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[CH:5][CH:4]=1
Reactant: COC(OC)OC
Reactant: COC(=O)c1ccc(C=O)cc1
Agent: O=S(=O)(O)O
Solvent: CO
Solvent: ClCCl
Product: COC(=O)c1ccc(C(OC)OC)cc1
Temperature: 25 °C
Reaction time: 16 h
Yield: 102.5 %

Procedure:
To a solution of methyl 4-formylbenzoate (CAS [1571-08-0] 5.33 g, 32.5 mmol) in methanol (40 mL) were added trimethyl orthoformate (7.5 mL, 68.25 mmol) and sulfuric acid (fuming, 3 drops). After heating to reflux with stirring for 16 h, the reaction mixture was cooled to RT and diluted with methylene chloride. The mixture was washed with a saturated solution of sodium bicarbonate and brine, dried over magnesium sulfate, and concentrated to afford 7 g of methyl 4-(dimethoxymethyl)benzoate as a colorless oil.
Reaction SMILES: [NH2:1][C:2]1[C:7]([N+:8]([O-:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[OH:11].C([O-])([O-])=O.[K+].[K+].I[CH:19]([CH3:21])[CH3:20]>CN(C=O)C>[CH:19]([O:11][C:3]1[CH:4]=[CH:5][CH:6]=[C:7]([N+:8]([O-:10])=[O:9])[C:2]=1[NH2:1])([CH3:21])[CH3:20]
Reactant: Nc1c(O)cccc1[N+](=O)[O-]
Reactant: CC(C)I
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CC(C)Oc1cccc([N+](=O)[O-])c1N
Temperature: 25 °C
Reaction time: 8 h

Procedure:
To a solution of 5 g of 2-amino-3-nitrophenol in 10 mL DMF were added 4.9 g of K2CO3 and 3.6 mL of 2-iodopropane. The reaction mixture was stirred at rt overnight and then concentrated in vacuo. The residue was taken up in sat. aq. NH4Cl and extracted with EtOAc (3 times). The organic phases were combined, washed with water, brine, dried over MgSO4 and concentrated in vacuo. Purification by CC with EtOAc-Hept (2:8) afforded 5.2 g of 2-isopropoxy-6-nitro-phenylamine as orange oil.
Reaction SMILES: [O:1]1[C:5]([C:6]2[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=2)=[CH:4][N:3]=[CH:2]1.[Li]CCCC.[C:17](Cl)(=[O:27])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26]>C1COCC1.CCOC(C)=O.[Cl-].[Cl-].[Zn+2]>[N:7]1[CH:8]=[CH:9][CH:10]=[CH:11][C:6]=1[C:5]1[O:1][C:2]([C:17](=[O:27])[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH3:26])=[N:3][CH:4]=1
Reactant: c1ccc(-c2cnco2)nc1
Reactant: CCCCCCCCCC(=O)Cl
Agent: [Cl-]
Agent: [Li]CCCC
Agent: [Zn+2]
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CCCCCCCCCC(=O)c1ncc(-c2ccccn2)o1
Reaction time: 0.33 h
Yield: 39.7 %

Procedure:
(187) A solution of 2-(oxazol-5-yl)pyridine (100 mg, 0.68 mmol) in anhydrous THF (5 mL) cooled to −75° C. under N2 was treated with n-BuLi (2.5 M in hexanes, 1.1 equiv, 0.75 mmol, 0.30 mL), and stirred for 20 min. ZnCl2 (0.5 M in THF, 2.0 equiv, 1.40 mmol, 2.8 mL) was added at −75° C., and stirred for 45 min at 0° C. Cul (1.0 equiv, 0.68 mmol, 130 mg) was added, and the solution was stirred for 10 min at 0° C. Decanoyl chloride (2 equiv, 1.4 mmol, 270 mg, 0.29 mL) was added and the solution was stirred for 1 h at 0° C. The reaction was diluted with EtOAc (10 mL), and washed with 15% aqueous NH4OH (1×10 mL), H2O (1×10 mL), and saturated aqueous NaCl (1×10 mL). The organic layer was dried (Na2SO4), filtered, and concentrated under reduced pressure. Flash chromatography (SiO2, 2.5 cm×17.5 cm, 20% EtOAc-hexanes) afforded 1-(5-(pyridin-2-yl)oxazol-2-yl)decan-1-one (187) (80 mg, 0.27 mmol, 40% yield) as a light brown powder: mp 56-57° C.; 1H NMR (CDCl3, 250 MHz) d 8.69-8.62 (m, 1H), 7.87-7.75 (m, 3H), 7.33-7.25 (m, 1H), 3.08 (t, J=7.7 Hz, 2H), 1.81-1.69 (m, 2H), 1.41-1.19 (m, 12H), 0.86 (br t, J=7.0 Hz, 3H); 13C NMR (CDCl3, 62.5 MHz) d 188.5, 157.3, 153.1, 150.0, 146.2, 136.9, 127.8, 124.1, 120.3, 39.1, 31.8, 29.4, 29.3, 29.2, 29.1, 24.0, 22.6, 14.0; IR (KBr) umax 2930, 2845, 1697, 1601, 1422, 1380 cm−1; MALDI-FTMS (DHB) m/z300.1911 (C18H24N2O2+H+ requires 301.1910).
Reaction SMILES: [CH2:1]([C:3]1[C:4]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[C:5]([CH:9]=[O:10])[NH:6][C:7]=1I)[CH3:2].FC1C=CC(B(O)O)=CC=1.[CH3:31][C:32]1[CH:33]=[C:34](B(O)O)[CH:35]=[CH:36][CH:37]=1>>[CH2:1]([C:3]1[C:4]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])=[C:5]([CH:9]=[O:10])[NH:6][C:7]=1[C:36]1[CH:35]=[CH:34][CH:33]=[C:32]([CH3:31])[CH:37]=1)[CH3:2]
Reactant: Cc1cccc(B(O)O)c1
Reactant: CCc1c(I)[nH]c(C=O)c1C(=O)OCc1ccccc1
Agent: OB(O)c1ccc(F)cc1
Product: CCc1c(-c2cccc(C)c2)[nH]c(C=O)c1C(=O)OCc1ccccc1

Procedure:
Following the procedures described in Example 5, replacing methyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylate with benzyl 4-ethyl-2-formyl-5-iodo-1H-pyrrole-3-carboxylate and 4-fluorophenylboronic acid with 3-methylphenylboronic acid, the title compound was obtained. Proton NMR for the product was consistent with the title compound. HRMS (ES) exact mass calculated for C22H22NO3 (M+H): 348.1594. Found 348.1611
Reaction SMILES: [H-].[Na+].[F:3][CH:4]([F:7])[CH2:5][OH:6].C(S[C:12]1[N:13]([C:24]2[CH:29]=[CH:28][C:27]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[CH:26][CH:25]=2)[C:14](=[O:23])[C:15]2[CH:21]=[CH:20][C:19](=[O:22])[NH:18][C:16]=2[N:17]=1)CC.O>O1CCCC1>[F:3][CH:4]([F:7])[CH2:5][O:6][C:12]1[N:13]([C:24]2[CH:25]=[CH:26][C:27]([O:30][CH2:31][C:32]([F:35])([F:34])[F:33])=[CH:28][CH:29]=2)[C:14](=[O:23])[C:15]2[CH:21]=[CH:20][C:19](=[O:22])[NH:18][C:16]=2[N:17]=1
Reactant: OCC(F)F
Reactant: CCCSc1nc2[nH]c(=O)ccc2c(=O)n1-c1ccc(OCC(F)(F)F)cc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Solvent: O
Product: O=c1ccc2c(=O)n(-c3ccc(OCC(F)(F)F)cc3)c(OCC(F)F)nc2[nH]1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To a suspension of sodium hydride (60% in oil, 36 mg) in tetrahydrofuran (5 ml) was added 2,2-difluoroethanol (0.095 ml) at room temperature, and the mixture was stirred at room temperature for 10 min. To the reaction mixture was added 2-(propylsulfanyl)-3-[4-(2,2,2-trifluoroethoxy)phenyl]pyrido[2,3-d]pyrimidine-4,7(3H,8H)-dione (123 mg), and the mixture was stirred at room temperature for 5 hr. The reaction mixture was added to water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and recrystallized from a mixed solvent of hexane/ethyl acetate to give the title compound (73 mg).
Reaction SMILES: [CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[NH:27][N:26]=[N:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]2[C:28]([CH2:32][C:33]([O:35]CC)=[O:34])=[CH:29][CH:30]=[CH:31][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]>[OH-].[Na+].CO>[CH2:1]([C:5]1[N:9]([CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=3[C:23]3[NH:27][N:26]=[N:25][N:24]=3)=[CH:13][CH:12]=2)[C:8]2[C:28]([CH2:32][C:33]([OH:35])=[O:34])=[CH:29][CH:30]=[CH:31][C:7]=2[N:6]=1)[CH2:2][CH2:3][CH3:4]
Reactant: CCCCc1nc2cccc(CC(=O)OCC)c2n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: CCCCc1nc2cccc(CC(=O)O)c2n1Cc1ccc(-c2ccccc2-c2nnn[nH]2)cc1
Yield: 45.4 %

Procedure:
A mixture of ethyl 2-butyl-1-[[2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]benzimidazole-7-acetate (0.28 g) in 1N NaOH (1.5 ml) and methanol (5 ml) was heated for two hours under reflux. The reaction mixture was concentrated, which was neutralized with 1N-HCl. Crystals separated out were collected by filtration and purified by column chromatography on silica gel to afford colorless crystals (0.12 g, 46%), m.p. 170°-171° C.
Reaction SMILES: [CH2:1]([O:4][C:5]1[CH:6]=[C:7]([CH:27]=[CH:28][C:29]=1[Cl:30])[O:8][C:9]1[CH:26]=[CH:25][C:12]([CH2:13][NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[C:16]=2[CH3:24])=[CH:11][CH:10]=1)[CH:2]=[CH2:3].[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>>[CH2:1]([O:4][C:5]1[CH:6]=[C:7]([CH:27]=[CH:28][C:29]=1[Cl:30])[O:8][C:9]1[CH:26]=[CH:25][C:12]([CH2:13][N:14]([CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([N+:21]([O-:23])=[O:22])[C:16]=2[CH3:24])=[CH:11][CH:10]=1)[CH:2]=[CH2:3]
Reactant: C=CCOc1cc(Oc2ccc(CNc3cccc([N+](=O)[O-])c3C)cc2)ccc1Cl
Reactant: BrCc1ccccc1
Product: C=CCOc1cc(Oc2ccc(CN(Cc3ccccc3)c3cccc([N+](=O)[O-])c3C)cc2)ccc1Cl

Procedure:
The product from Example 91D and benzyl bromide was processed as described in Example 6B to provide the title compound.
Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].C[N:8]1[CH2:12][CH2:11][CH2:10][C:9]1=[O:13]>>[NH:1]1[CH2:5][CH2:4][CH2:3][C:2]1=[O:6].[CH3:2][CH:12]1[NH:8][C:9](=[O:13])[CH2:10][CH2:11]1
Reactant: CN1CCCC1=O
Agent: O=C1CCCN1
Product: CC1CCC(=O)N1

Procedure:
In general, even a minimal amount of 2-oxo-1-pyrrolidinyl groups in the reaction admixture of lactam, lactam polymerization initiator and lactam polymerization catalyst is effective in increasing the polymerization rate. The 2-oxo-1-pyrrolidinyl compounds can be any one of 2-pyrrolidinone, initiator compound capped with 2-oxo-1-pyrrolidinyl groups and 2-oxo-1-pyrrolidinyl magnesium halide and can therefor be added in the lactam initiator solution or in the catalyst stream or in both. Preferably all the 2-oxo-1-pyrrolidinyl compound is added in the initiator stream and more preferably it is all present as 2-oxo-1-pyrrolidinyl capped initiator. In contrast to 2-pyrrolidinone, other derivatives of pyrrolidinone such as N-methyl-2-pyrrolidinone and 5-methyl-2-pyrrolidinone provided no accelerating effect.
Reaction SMILES: [CH:1]1([CH2:4][O:5][C:6]2[N:11]=[C:10]([C:12]([OH:14])=O)[CH:9]=[CH:8][C:7]=2[N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH2:3][CH2:2]1.[CH3:20][C:21]([NH2:31])([CH3:30])[CH2:22][CH2:23][N:24]1[CH2:29][CH2:28][O:27][CH2:26][CH2:25]1>>[CH3:30][C:21]([NH:31][C:12]([C:10]1[CH:9]=[CH:8][C:7]([N:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)=[C:6]([O:5][CH2:4][CH:1]2[CH2:2][CH2:3]2)[N:11]=1)=[O:14])([CH3:20])[CH2:22][CH2:23][N:24]1[CH2:25][CH2:26][O:27][CH2:28][CH2:29]1
Reactant: O=C(O)c1ccc(N2CCCC2)c(OCC2CC2)n1
Reactant: CC(C)(N)CCN1CCOCC1
Product: CC(C)(CCN1CCOCC1)NC(=O)c1ccc(N2CCCC2)c(OCC2CC2)n1

Procedure:
The title compound was synthesized in analogy to Example 1, using 6-cyclopropylmethoxy-5-pyrrolidin-1-yl-pyridine-2-carboxylic acid (Example 14 a) and 1,1-dimethyl-3-morpholin-4-yl-propylamine as starting materials, MS (EI): 417.2 [M+H]+.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:24])[CH2:5][C:6]1[CH:7]=[N:8][N:9](CC2C=CC=CC=2)[C:10]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)[CH3:2].C(O)=O>[C].[Pd].C(O)C>[C:11]1([C:10]2[C:6]([CH2:5][C:4]([O:3][CH2:1][CH3:2])=[O:24])=[CH:7][NH:8][N:9]=2)[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: CCOC(=O)Cc1cnn(Cc2ccccc2)c1-c1ccccc1
Agent: [Pd]
Solvent: CCO
Solvent: O=CO
Product: CCOC(=O)Cc1c[nH]nc1-c1ccccc1
Yield: 90.1 %

Procedure:
A mixture of ethyl(1-benzyl-5-phenyl-1H-pyrazol-4-yl)acetate (3.60 g), 5% palladium-carbon (7.00 g), formic acid (40 ml), and ethanol (150 ml) was refluxed for 2 hours. After the palladium-carbon was removed by filtration, the filtrate was concentrated. The residue was dissolved in ethyl acetate, washed with saturated aqueous sodium bicarbonate and then with saturated aqueous sodium chloride solution, dried (MgSO4), and concentrated to obtain ethyl (3-phenyl-1H-pyrazol-4-yl)acetate (2.33 g, yield: 90%) as a colorless oily substance.
Reaction SMILES: [H-].[Na+].C[O:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[N:20]=[C:19]([NH:21][CH2:22][C:23]2[O:24][C:25]([CH3:28])=[N:26][N:27]=2)[C:18]2[C:13](=[CH:14][C:15]([CH3:29])=[CH:16][CH:17]=2)[N:12]=1.[CH3:30]I>CN(C=O)C>[CH3:29][C:15]1[CH:14]=[C:13]2[C:18]([C:19]([N:21]([CH3:30])[CH2:22][C:23]3[O:24][C:25]([CH3:28])=[N:26][N:27]=3)=[N:20][C:11]([C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][C:5]=3[OH:4])=[N:12]2)=[CH:17][CH:16]=1
Reactant: CI
Reactant: COc1ccccc1-c1nc(NCc2nnc(C)o2)c2ccc(C)cc2n1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cc1ccc2c(N(C)Cc3nnc(C)o3)nc(-c3ccccc3O)nc2c1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 66 %

Procedure:
[2-(2-Methoxy-phenyl)-7-methyl-quinazolin-4-yl]-methyl-(5-methyl-[1,3,4]oxadiazol-2-ylmethyl)-anine To a stirring suspension of freshly washed sodium hydride (42 mg, 1.04 mmol) in dry DMF at 0° C. under a nitrogen atmosphere was added the [2-(2-Methoxy-phenyl)-7-methyl-quinazolin-4-yl]-(5-methyl-[1,3,4]oxadiazol-2-ylmethyl)-amine (180 mg, 0.518 mmol, in 5 ml DMF). After 30 minutes at 0° C., MeI (74 μl, 1.19 mmol) was added and the reaction was allowed to warm to room temperature. After one hour the reaction was quenched with water and extracted 3 times with EtOAc. Organics were combined, dried over MgSO4, filtered and concentrated to a yellow oil. Purified by flash chromatography 50/50 EtOAc/hexanes to afford the desired product as a clear oil. 128 mg, 66% yield. LC/MS (10-99%) M/Z 376.1, retention time 2.06 minutes.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][C:11](O)([C:13]([F:16])([F:15])[F:14])[N:10]=[C:9]2[C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:26])=[O:25])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH:12]=[C:11]([C:13]([F:16])([F:14])[F:15])[N:10]=[C:9]2[C:18]2[CH:23]=[CH:22][C:21]([S:24]([CH3:27])(=[O:25])=[O:26])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1
Reactant: CS(=O)(=O)c1ccc(C2=NC(O)(C(F)(F)F)CN2c2ccc(F)cc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CS(=O)(=O)c1ccc(-c2nc(C(F)(F)F)cn2-c2ccc(F)cc2)cc1
Yield: 44.9 %

Procedure:
A mixture of 1-(4-fluorophenyl)-4-hydroxy-2-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-4,5-dihydro-1H-imidazole (Example 3) (770 mg, 1.9 mmol) and p-toluenesulfonic acid monohydrate (88 mg) in toluene (80 mL) was heated to reflux for 20 hours. The reaction mixture was cooled and the solvent removed under reduced pressure. The crude residue was redissolved in methylene chloride and washed with water, aqueous sodium bicarbonate and brine. After drying (Na2SO4), filtration and concentration in vacuo, the crude mixture (520 mg) was chromatographed on silica gel using hexane/ethyl acetate (1/1) to give pure 1-(4-fluorophenyl)-2-[4-(methylsulfonyl)phenyl]-4-(trifluoromethyl)-1H-imidazole (328 mg, 44%) as a white solid: mp (DSC) 183° C. Anal. Calc'd. for C17H12N2SO2F4 : C, 53.13, H, 3.15, N, 7.29. Found: C, 53.20, H, 3.22, N, 7.18.
Reaction SMILES: Cl[C:2]1[N:10]([CH3:11])[C:5]2=[N:6][CH:7]=[CH:8][CH:9]=[C:4]2[N:3]=1.[CH2:12]([N:14]1[C:22]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:16]([C:23]2[CH:28]=[CH:27][C:26]([OH:29])=[CH:25][CH:24]=2)[C:15]1=[O:30])[CH3:13].[H-].[Na+].[Cl-].[Cl-].[Ca+2].Cl>CN(C=O)C>[CH2:12]([N:14]1[C:22]2[C:17](=[N:18][CH:19]=[CH:20][CH:21]=2)[N:16]([C:23]2[CH:24]=[CH:25][C:26]([O:29][C:2]3[N:10]([CH3:11])[C:5]4=[N:6][CH:7]=[CH:8][CH:9]=[C:4]4[N:3]=3)=[CH:27][CH:28]=2)[C:15]1=[O:30])[CH3:13]
Reactant: CCn1c(=O)n(-c2ccc(O)cc2)c2ncccc21
Reactant: Cn1c(Cl)nc2cccnc21
Agent: Cl
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CN(C)C=O
Product: CCn1c(=O)n(-c2ccc(Oc3nc4cccnc4n3C)cc2)c2ncccc21
Yield: 58 %

Procedure:
2-Chloro-3-methyl-3H-imidazo[4,5-b]pyridine (150 mg) was added to a solution of 1-ethyl-3-(4-hydroxyphenyl)-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (228 mg) and NaH (39.4 mg) in DMF (2 mL) at 100° C. The mixture was stirred at 180° C. under a dry atmosphere (CaCl2 tube) for 1 h. The mixture was neutralized with 1N HCl at 0° C. and extracted with EtOAc. The organic layer was separated, washed with water and brine, dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (NH silica gel, eluted with 0%-100% EtOAc in hexane) to give 1-ethyl-3-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one (200 mg) as white crystals.
Reaction SMILES: Cl[C:2]1[C:7]2[CH:8]=[CH:9][NH:10][C:6]=2[CH:5]=[CH:4][N:3]=1.C([Sn](CCCC)(CCCC)[C:16]([O:18]CC)=[CH2:17])CCC.Cl>CN1C(=O)CCC1.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>[NH:10]1[C:6]2[CH:5]=[CH:4][N:3]=[C:2]([C:16](=[O:18])[CH3:17])[C:7]=2[CH:8]=[CH:9]1
Reactant: Clc1nccc2[nH]ccc12
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Solvent: CN1CCCC1=O
Product: CC(=O)c1nccc2[nH]ccc12
Temperature: 140 °C
Reaction time: 18 h
Yield: 64.5 %

Procedure:
A mixture of 4-chloro-1H-pyrrolo[3,2-c]pyridine (1.0 g, 6.58 mmol), Pd(PPh3)4 (763 mg, 0.66 mmol), and tributyl(1-ethoxyvinyl)stannane (2.61 g, 7.23 mmol) in NMP (20 mL) was stirred under N2 at 140° C. for 18 h. The reaction mixture was poured into aqueous HCl solution (2 N, 150 mL), stirred at RT for 2 h, and washed with DCM (50 mL×3). The aqueous layer was adjusted to pH 8 with NaHCO3 (solid), extracted with EtOAc (50 mL×3), and concentrated under reduced pressure to afford 680 mg (64.6%) of 1-(1H-pyrrolo[3,2-c]pyridin-4-yl)ethanone as yellow solid: MS (ESI) nilz: 161.1 [M+1]+.