Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([O:5][CH2:6][CH:7]([O:17][CH2:18][CH2:19][O:20][CH2:21][CH2:22][CH2:23][CH3:24])[CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH3:16])(C)(C)C.ClCCl.C(=O)([O-])[O-].[K+].[K+]>C(OCC)C>[CH2:21]([O:20][CH2:19][CH2:18][O:17][CH:7]([CH2:8][O:9][CH2:10][CH2:11][O:12][CH2:13][CH2:14][CH2:15][CH3:16])[CH2:6][OH:5])[CH2:22][CH2:23][CH3:24]
Reactant: CCCCOCCOCC(COC(C)(C)C)OCCOCCCC
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: ClCCl
Solvent: CCOCC
Product: CCCCOCCOCC(CO)OCCOCCCC

Procedure:
Compound 31 was prepared as described for 29. The reagents used were as follows, compound 25 (38.0 g, 0.109 mol.), tetrafluoroboric acid-diethyl ether complex (22 ml of a 54% solution in diethyl ether) dichloromethane (100 ml) and excess potassium carbonate. The final yield was a colorless liquid (17.3 g, 59%), (bpt. 95°-120° C., 0.04 torr): 1H-NMR (CDCl3), d, (ppm). Mass spectroscopy, m/e 293 MH+.
Reaction SMILES: [NH2-:1].[Na+].C(O)(=O)CCCCCCC/C=C\CCCCCCCC.[CH3:23][CH2:24][CH:25]([C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][N:29]=1)[CH2:26][CH3:27].[H][H]>O.C1(C)C(C)=CC=CC=1>[NH2:1][C:30]1[CH:31]=[CH:32][CH:33]=[C:28]([CH:25]([CH2:26][CH3:27])[CH2:24][CH3:23])[N:29]=1
Reactant: CCC(CC)c1ccccn1
Reactant: [H][H]
Reactant: [NH2-]
Agent: CCCCCCCC/C=C\CCCCCCCC(=O)O
Agent: [Na+]
Solvent: Cc1ccccc1C
Solvent: O
Product: CCC(CC)c1cccc(N)n1
Temperature: 190 °C
Yield: 99.6 %

Procedure:
A mixture of 105.8 g (2.71 moles) of sodamide and 332 g of xylene containing 1.0 cc of oleic acid was placed in a liter Magne Drive, equipped as described in Example 15. The autoclave was closed and purged of air with nitrogen and pressurized to 100 psig with nitrogen. The pressure relief valve was set at 100 psig. Cooling water was turned on the reflux condenser. The mixture was heated with stirring to 190° C. and 235.0 g (1.58 moles) of 2-(3-pentyl)pyridine was started adding from a Fisher-porter pressure bottle. The addition required 5.5 hours at 190° C.-215° C. The reaction mixture was heated an additional 5 hours within that temperature range until hydrogen almost stopped passing through the relief valve. The autoclave was cooled to 50° C., vented to atmospheric pressure and hydrolyzed with 200 cc of water. The oil layer was separated and distilled under vacuum to give 258.6 g of 2 -amino-6-(3-pentyl)pyridine. b.p. 163° C. at 60 mm. n25D 1.5357 (yield 68.1%). This 2-amino-6-pentyl)pyridine is a new composition of matter. It is a novel liquid aminopyridine and has valuable biocidal properties. When this amination is repeated at atmospheric pressure under classic Chichibabin conditions, the product is 6,6'-di-(3-pentyl)-2,2'-bipyridyl as shown in McGill, U.S. Pat. No. 4,177,349 (1979) and McGill, U.S. Pat. No. 4,267,335 (1981).
Reaction SMILES: [NH2:1][C:2]1[C:3]([N:9]2[CH2:14][CH2:13][N:12]([C:15](=[O:24])[CH2:16][N:17]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[N:18]3)[CH2:11][CH2:10]2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:25][C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29](Cl)=[O:30].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:25][C:26]1[CH:27]=[C:28]([CH:32]=[CH:33][CH:34]=1)[C:29]([NH:1][C:2]1[C:3]([N:9]2[CH2:10][CH2:11][N:12]([C:15](=[O:24])[CH2:16][N:17]3[C:21]([CH3:22])=[CH:20][C:19]([CH3:23])=[N:18]3)[CH2:13][CH2:14]2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1)=[O:30]
Reactant: O=C(Cl)c1cccc(Cl)c1
Reactant: Cc1cc(C)n(CC(=O)N2CCN(c3ncc(Cl)cc3N)CC2)n1
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Product: Cc1cc(C)n(CC(=O)N2CCN(c3ncc(Cl)cc3NC(=O)c3cccc(Cl)c3)CC2)n1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of 1-[4-(3-amino-5-chloro-pyridin-2-yl)-piperazin-1-yl]-2-(3,5-dimethyl-pyrazol-1-yl)-ethanone (0.040 g, 0.11 mmol) in methylene chloride (2 mL) is added 3-chlorobenzoyl chloride (0.020 mL, 0.160 mmol) followed by of N,N-diisopropylethylamine (0.045 mL, 0.25 mmol). The mixture is stirred at room temperature for 3 days. The mixture is concentrated under a stream of nitrogen and the residue is purified by preparative reverse phase HPLC to provide, after removal of the eluent under reduced pressure, 0.030 g of 3-chloro-N-(5-chloro-2-{4-[2-(3,5-dimethyl-pyrazol-1-yl)-acetyl]-piperazin-1-yl}-pyridin-3-yl)-benzamide as a white solid in 53% yield. MS; MH+=487.7
Reaction SMILES: [Br:1][C:2]1[C:15]2[CH:14]=[CH:13][C:12]3[N:11]=[C:10](NC(=O)C(C)(C)C)[NH:9][C:8](=[O:23])[C:7]=3[C:6]=2[CH:5]=[CH:4][CH:3]=1.[CH2:24]([NH2:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CCOCC>[CH2:24]([NH:31][C:10]1[NH:9][C:8](=[O:23])[C:7]2[C:6]3[CH:5]=[CH:4][CH:3]=[C:2]([Br:1])[C:15]=3[CH:14]=[CH:13][C:12]=2[N:11]=1)[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: NCc1ccccc1
Reactant: CC(C)(C)C(=O)Nc1nc2ccc3c(Br)cccc3c2c(=O)[nH]1
Solvent: CCOCC
Product: O=c1[nH]c(NCc2ccccc2)nc2ccc3c(Br)cccc3c12

Procedure:
A mixture of N-(7-bromo-1,2-dihydro-1-oxobenzo[f]quinazolin-3-yl)pivalamide (0.3 g, 0.8 mmole) and benzylamine (10 ml) was stirred and heated at reflux under a nitrogen atmosphere for 18 hours. The cooled reaction mixture was then mixed with 4 volumes of ether to cause precipitation of the product. The precipitate was filtered and recrystallized from methanol to give 3-(benzylamino)-7-bromobenzo-[f]quinazolin-1(2H)-one as an off-white solid. (0.11 g, 37%) 1H NMR (DMSO-d6, 200 MHz) δ: 4.62(d, J=5.7 Hz, 2H, CH2); 7.02(m, 1H, benzyl-NH); 7.20-7.55(m, 7H, Ar); 7.79(dd, J=7.5, 1.1 Hz, 1H, Ar); 8.30(d, J=9.2 Hz, 1H, Ar); 9.74(d, J=8.6 Hz, 1H, Ar); 11.2(br s, 1H, pyr-NH).
Reaction SMILES: [CH3:1][O:2][CH:3]([O:6][CH3:7])[CH:4]=O.[NH2:8][OH:9].C1C(=O)N(Cl)C(=O)C1.[CH2:18]=[C:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:7][O:6][CH:3]([O:2][CH3:1])[C:4]1[CH2:18][C:19]2([CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]2)[O:9][N:8]=1
Reactant: C=C1CCCCC1
Reactant: COC(C=O)OC
Reactant: NO
Agent: O=C1CCC(=O)N1Cl
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: COC(OC)C1=NOC2(CCCCC2)C1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a 40 mL vial equipped with a magnetic stir bar was added DMF (10 mL) and dimethoxy-acetaldehyde (1.50 mL, 10.0 mmol). Aqueous hydroxylamine (0.640 mL, 10.5 mmol) was added via syringe, and the mixture was stirred for 2 h at rt. NCS (1.40 g, 10.5 mmol) was added in small portions as a solid. The mixture was stirred an additional 1 h at rt, diluted with DCM (40 mL), dried over MgSO4, and filtered. The solid was washed with DCM. The filtrate was diluted to a volume of 100 mL and transferred to two 60 mL syringes. Methylene-cyclohexane (2.40 mL, 20.0 mmol), DIPEA (1.92 mL, 11.0 mmol), and DCM (10 mL) were placed in a 200 mL round-bottom flask equipped with a magnetic stir bar. The above-prepared chlorooxime solution was added dropwise with a syringe pump at a rate of 0.0774 mL/min until the addition was complete. The mixture stirred at rt for 3 days, and the solvent was removed under reduced pressure. The residue was dissolved in water (50 mL) and extracted three times with hexanes (25 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The material was used in the next step without purification.
Reaction SMILES: [NH:1]1[CH:5]=[CH:4][C:3]([NH2:6])=[N:2]1.C(OC(N1[C:20](=[O:21])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[C:13]1=[O:22])=O)C>C1COCC1>[NH:1]1[CH:5]=[CH:4][C:3]([N:6]2[C:20](=[O:21])[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[C:13]2=[O:22])=[N:2]1
Reactant: CCOC(=O)N1C(=O)c2ccccc2C1=O
Reactant: Nc1cc[nH]n1
Solvent: C1CCOC1
Product: O=C1c2ccccc2C(=O)N1c1cc[nH]n1

Procedure:
1H-Pyrazol-3-ylamine (2 g, 24 mmol) and 1,3-dioxo-1,3-dihydro-isoindole-2-carboxylic acid ethyl ester (5.3 g, 24 mmol) are stirred in THF (70 ml) at room temperature for 18 hours. The reaction mixture is then concentrated to half volume and filtered to remove the titled compound which is washed with methanol followed by diethyl ether.
Reaction SMILES: C([O-])([O-])=O.[K+].[K+].[CH3:7][N:8]([CH:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1)[C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([CH2:16]Br)=[CH:12][CH:11]=1.[CH3:25][O:26][C:27]1[CH:28]=[C:29]([OH:33])[CH:30]=[CH:31][CH:32]=1>>[CH:19]1([N:8]([CH3:7])[C:9](=[O:18])[C:10]2[CH:15]=[CH:14][C:13]([CH2:16][O:33][C:29]3[CH:30]=[CH:31][CH:32]=[C:27]([O:26][CH3:25])[CH:28]=3)=[CH:12][CH:11]=2)[CH2:24][CH2:23][CH2:22][CH2:21][CH2:20]1
Reactant: COc1cccc(O)c1
Reactant: CN(C(=O)c1ccc(CBr)cc1)C1CCCCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1cccc(OCc2ccc(C(=O)N(C)C3CCCCC3)cc2)c1

Procedure:
The reaction and workup were carried out in the same manner as for Example 21 using K2CO3 (674 mg, 4.88 mmol), 4-bromomethylbenzoic acid N-methyl-N-cyclohexyl amide (629 mg, 2.03 mmol) and 3-methoxyphenol (251 mg, 2.02 mmol). The crude product was chromatographed on silica gel using mixtures of ethyl acetate and hexane as eluents to give the title compound as a crystalline solid that could be recrystallized from ethyl acetate and hexane, m. pt. 90.38° C. (DSC).
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:18]=[C:19]([O:21][CH2:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=2[CH3:29])[CH:20]=1)[C:5]([NH:7][C:8]1[N:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=1)=[O:6].[I-].[K+].C(=O)([O-])[O-].[K+].[K+].Cl[CH2:39][C:40]1[CH:44]=[C:43]([CH3:45])[O:42][N:41]=1>CC(C)=O.C(OCC)(=O)C>[CH3:29][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=1[CH2:22][O:21][C:19]1[CH:18]=[C:4]([CH:3]=[C:2]([O:1][CH2:39][C:40]2[CH:44]=[C:43]([CH3:45])[O:42][N:41]=2)[CH:20]=1)[C:5]([NH:7][C:8]1[N:13]=[CH:12][C:11]([C:14]([O:16][CH3:17])=[O:15])=[CH:10][CH:9]=1)=[O:6]
Reactant: Cc1cc(CCl)no1
Reactant: COC(=O)c1ccc(NC(=O)c2cc(O)cc(OCc3ccccc3C)c2)nc1
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CC(C)=O
Solvent: CCOC(C)=O
Product: COC(=O)c1ccc(NC(=O)c2cc(OCc3cc(C)on3)cc(OCc3ccccc3C)c2)nc1
Temperature: 55 °C
Reaction time: 1 h
Yield: 135.2 %

Procedure:
Methyl 6-{[3-hydroxy-5-(2-methylbenzyloxy)benzoyl]amino}-3-pyridinecarboxylate (150 mg, 0.38 mM), potassium iodide (13 mg, 0.08 mM) and potassium carbonate (56 mg, 0.41 mM) in acetone (3 ml) were heated to 55° C. and a solution of 3-chloromethyl-5-methyl isoxazole (55 mg, 0.421 mM) in acetone (2 ml) was added. The reaction was stirred for 1 hour at 55° C. and a further addition of 3-chloromethyl-5-methyl isoxazole (33 mg, 0.25 mM) in acetone (1 ml) was made. The reaction was stirred for 24 hours at 55° C. before being allowed to cool to ambient temperature. Ethyl acetate (15 ml) was added and the resulting mixture was washed with 1N aqueous HCl (10 ml), saturated aqueous sodium bicarbonate solution (10 ml) and water (10 ml). The solvent was removed under reduced pressure to give methyl 6{[3-(2-methylbenzyloxy)-5-(5-methylisoxazol-3-ylmethoxy)benzoyl]amino}-3-pyridinecarboxylate as a white solid (252 mg); H1 NMR δ (d6-DMSO) 2.24 (3H s) 2.26 (3H s) 3.85 (3H s) 5.08 (2H s) 5.15 (s 2H) 6.28–6.35 (1H m) 6.88 (1H s) 7.17–7.43 (7H, m), 8.29 (1H s), 8.9 (11H d). MS [MH]+488
Reaction SMILES: Cl[C:2]1[N:12]=[C:11]2[C:5]([N:6]([CH3:19])[C:7](=[O:18])[CH2:8][CH2:9][N:10]2[CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])=[CH:4][N:3]=1.[NH2:20][C:21]1[CH:36]=[CH:35][C:24]([C:25]([NH:27][CH:28]2[CH2:33][CH2:32]N(C)[CH2:30][CH2:29]2)=[O:26])=[CH:23][C:22]=1[O:37][CH3:38].O.[C:40]1(C)C=CC(S(O)(=O)=O)=CC=1.CO>CC(O)C>[CH:28]1([NH:27][C:25](=[O:26])[C:24]2[CH:35]=[CH:36][C:21]([NH:20][C:2]3[N:12]=[C:11]4[C:5]([N:6]([CH3:19])[C:7](=[O:18])[CH2:8][CH2:9][N:10]4[CH2:13][CH2:14][N:15]([CH3:17])[CH3:16])=[CH:4][N:3]=3)=[C:22]([O:37][CH3:38])[CH:23]=2)[CH2:29][CH2:30][CH2:40][CH2:32][CH2:33]1
Reactant: Cc1ccc(S(=O)(=O)O)cc1
Reactant: COc1cc(C(=O)NC2CCN(C)CC2)ccc1N
Reactant: CN(C)CCN1CCC(=O)N(C)c2cnc(Cl)nc21
Solvent: CC(C)O
Solvent: O
Solvent: CO
Product: COc1cc(C(=O)NC2CCCCC2)ccc1Nc1ncc2c(n1)N(CCN(C)C)CCC(=O)N2C
Yield: 39.7 %

Procedure:
10-chloro-2-(2-dimethylaminoethyl)-6-methyl-2,6,9,11-tetrazabicyclo[5.4.0]undeca-7,9,11-trien-5-one (Intermediate 158; 84 mg, 0.30 mmol), 4-amino-3-methoxy-N-(1-methyl-4-piperidyl)benzamide (WO06/018220; 90 mg, 0.36 mmol) and p-toluenesulphonic acid monohydrate (113 mg, 0.60 mmol) were heated together in IPA (4 mL) by microwave irradiation at 150° C. for 20 minutes. The reaction mixture was loaded onto an SCX-2 (5 g) column pre-wet with methanol; the column was washed with methanol and the product eluted with 2M NH3/MeOH. Product containing fractions were combined and evaporated. The resultant material was purified by base modified reverse phase preparative HPLC to yield the title compound as a white solid (59 mg, 40%).
Reaction SMILES: [C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[S:17][C:18]4[C:28]5C(=CC(C=C)=[CH:26][CH:27]=5)[CH2:22][CH2:21][C:19]=4[N:20]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C[N+]1([O-])CC[O:35][CH2:34]C1.[CH2:39]1[CH2:43][O:42][CH2:41][CH2:40]1>[Os](=O)(=O)(=O)=O>[C:1]1([C:7]2[C:11]([C:12]([F:15])([F:14])[F:13])=[C:10]([C:16]3[S:17][C:18]4[C:28]5[C:41](=[CH:40][C:39]([CH:43]([OH:42])[CH2:34][OH:35])=[CH:26][CH:27]=5)[CH2:22][CH2:21][C:19]=4[N:20]=3)[O:9][N:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=Cc1ccc2c(c1)CCc1nc(-c3onc(-c4ccccc4)c3C(F)(F)F)sc1-2
Reactant: C[N+]1([O-])CCOCC1
Reactant: C1CCOC1
Agent: O=[Os](=O)(=O)=O
Product: OCC(O)c1ccc2c(c1)CCc1nc(-c3onc(-c4ccccc4)c3C(F)(F)F)sc1-2
Reaction time: 8 h

Procedure:
To 3-phenyl-4-(trifluoromethyl)-5-(7-vinyl-4,5-dihydronaphtho[2,1-d]thiazol-2-yl)isoxazole (Preparation 82E, 0.2 g, 0.471 mmol) in THF (3 mL) were sequentially added osmium tetroxide (4% aq.) (0.148 mL, 0.019 mmol) and NMO (50% aq.) (0.22 mL, 0.471 mmol) at room temperature and the contents were stirred overnight under a nitrogen atmosphere. The same reaction was setup in a different flask. The reaction mixtures from both flasks were combined and concentrated. The residue was partitioned between dichloromethane (40 mL) and water (10 mL). The dichloromethane layer was separated, dried over sodium sulfate and concentrated. To the solid was added acetonitrile (10 mL), the contents were triturated, sonicated and filtered. The solid was washed with acetonitrile (2×3 mL) and dried to yield 240 mgs of a pale yellow solid. The filtrate was concentrated and purified by silica gel column chromatography using an ISCO setup. (24 g, RediSep® silica gel column). The desired fractions were collected and concentrated to yield another 55 mgs of a pale yellow solid. The compound had an HPLC retention time=3.69 min. (condition C); LC/MS M+1=459; 1H NMR (400 MHz, CDCl3) δ ppm 7.66 (2H, d, J=6.6 Hz), 7.48-7.58 (3H, m), 7.41 (1H, d, J=7.7 Hz), 7.28-7.36 (2H, m), 4.82-4.90 (1H, m), 3.83 (1H, ddd, J=11.0, 7.3, 3.5 Hz), 3.71 (1H, td, J=7.5, 4.0 Hz), 3.13-3.25 (4H, m), 2.63 (1H, OH, d, J=3.3 Hz).
Reaction SMILES: C([N:8]1[CH2:22][CH2:21][C:11]2([O:15][C:14](=[O:16])[N:13]([C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:12]2)[CH2:10][CH2:9]1)C1C=CC=CC=1>[Pd].C(O)C>[C:17]([N:13]1[CH2:12][C:11]2([CH2:21][CH2:22][NH:8][CH2:9][CH2:10]2)[O:15][C:14]1=[O:16])([CH3:20])([CH3:18])[CH3:19]
Reactant: CC(C)(C)N1CC2(CCN(Cc3ccccc3)CC2)OC1=O
Agent: [Pd]
Solvent: CCO
Product: CC(C)(C)N1CC2(CCNCC2)OC1=O
Reaction time: 6.5 h
Yield: 113.1 %

Procedure:
A mixture of 8-benzyl-3-tert-butyl-3,8-diaza-1-oxaspiro[4.5]decane-2-one (9 g, 30 mmol), 10% palladium on carbon (0.9 g) and ethanol (100 mL) was stirred 6 to 7 hours under a hydrogen atmosphere (50 psi). The mixture was filtered and then concentrated to give crude 3-tert-butyl-3,8-diaza-1-oxaspiro[4.5]decane-2-one (7.2 g), m.p. 108°-111° C.
Reaction SMILES: CC1CCCCC1.[F:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=O)=[CH:11][CH:10]=1.[CH3:17][C:18]([C:20]1[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=1)=[O:19]>Cl>[F:8][C:9]1[CH:16]=[CH:15][C:12]([CH:13]=[CH:17][C:18]([C:20]2[CH:25]=[CH:24][C:23]([C:26]([F:27])([F:28])[F:29])=[CH:22][CH:21]=2)=[O:19])=[CH:11][CH:10]=1
Reactant: CC(=O)c1ccc(C(F)(F)F)cc1
Reactant: O=Cc1ccc(F)cc1
Agent: Cl
Solvent: CC1CCCCC1
Product: O=C(C=Cc1ccc(F)cc1)c1ccc(C(F)(F)F)cc1
Temperature: 12.5 °C

Procedure:
8 l of methylcyclohexane are initially charged and 3000 g of 4-fluorobenzaldehyde, 5000 g of 4-trifluoromethylacetophenone and 150 ml of conc. hydrochloric acid are added. The mixture is distilled azeotropically for approximately 8 hours until no more water separates off. After cooling to 10 to 15° C., the precipitated solid is filtered off with suction and washed with cold methylcyclohexane.
Reaction SMILES: [CH3:1][N:2]1[C:6]2=[N:7][CH:8]=[CH:9][CH:10]=[C:5]2[N:4]=[C:3]1S(C)(=O)=O.[OH:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[C:26]3=[N:27][CH:28]=[CH:29][CH:30]=[C:25]3[C:24]([CH3:32])([CH3:31])[C:23]2=[O:33])=[CH:18][CH:17]=1.[H-].[Na+]>CN(C=O)C.CO>[CH3:31][C:24]1([CH3:32])[C:25]2[C:26](=[N:27][CH:28]=[CH:29][CH:30]=2)[N:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][C:3]3[N:2]([CH3:1])[C:6]4=[N:7][CH:8]=[CH:9][CH:10]=[C:5]4[N:4]=3)=[CH:17][CH:18]=2)[C:23]1=[O:33]
Reactant: CC1(C)C(=O)N(c2ccc(O)cc2)c2ncccc21
Reactant: Cn1c(S(C)(=O)=O)nc2cccnc21
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CO
Product: Cn1c(Oc2ccc(N3C(=O)C(C)(C)c4cccnc43)cc2)nc2cccnc21
Temperature: 180 °C
Yield: 73.1 %

Procedure:
3-Methyl-2-(methylsulfonyl)-3H-imidazo[4,5-b]pyridine (90 mg) was added to a solution of 1-(4-hydroxyphenyl)-3,3-dimethyl-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (119 mg) and NaH (20.45 mg) in DMF (2 mL) at 100° C. The mixture was heated at 180° C. for 30 min under microwave irradiation. The reaction mixture was diluted with MeOH and concentrated under reduced pressure. The residue was purified by column chromatography (NH silica gel, eluted with 0%-50% EtOAc in hexane) to give 3,3-dimethyl-1-{4-[(3-methyl-3H-imidazo[4,5-b]pyridin-2-yl)oxy]phenyl}-1,3-dihydro-2H-pyrrolo[2,3-b]pyridin-2-one (120 mg) as white crystals.
Reaction SMILES: [C:1]1(=[O:6])O[CH2:4][CH2:3][CH2:2]1.[CH2:7]([NH2:19])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]>>[CH2:7]([N:19]1[CH2:4][CH2:3][CH2:2][C:1]1=[O:6])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18]
Reactant: O=C1CCCO1
Reactant: CCCCCCCCCCCCN
Product: CCCCCCCCCCCCN1CCCC1=O
Yield: 80.5 %

Procedure:
Following Example 5, 18.8 g (0.22M) of butyrolactone and 37 g (0.2M) of n-dodecylamine was heated for 24 hours. Distillation of the residue gave 40.7 g (80.3%) of 1-n-dodecylazacyclopentan-2-one; b.p. 165°-170°/0.5 mm.
Reaction SMILES: [C:1]([OH:5])(=[O:4])[CH:2]=O.[CH2:6]([C:8]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH3:16])[C:9]=1[NH2:10])[CH3:7].[CH:17](O)=[O:18]>>[CH2:6]([C:8]1[CH:14]=[CH:13][CH:12]=[C:11]([CH2:15][CH3:16])[C:9]=1[N:10]([CH:17]=[O:18])[CH2:2][C:1]([OH:5])=[O:4])[CH3:7]
Reactant: O=CC(=O)O
Reactant: O=CO
Reactant: CCc1cccc(CC)c1N
Product: CCc1cccc(CC)c1N(C=O)CC(=O)O
Temperature: 70 °C
Reaction time: 1 h

Procedure:
32.6 g (0.22 mole) of an approximately 50% strength aqueous glyoxylic acid solution were added dropwise to 14.9 g (0.10 mole) of 2,6-diethylaniline and 100 ml of formic acid at room temperature, with gentle warming. The mixture was stirred at 70° C. for 1 hour, with vigorous evolution of gas, the formic acid was distilled off up to an internal temperature of 120° C., the mixture was allowed to cool and was poured onto water and the solid was filtered off with suction and dired. 21.8 g of N-(2,6-diethylphenyl)-N-formylglycine of melting point 139-41° C. were obtained.
Reaction SMILES: C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][CH:11]=[C:10]([Cl:15])[CH:9]=2)=O)C.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C(OCC)C>[Cl:15][C:10]1[CH:9]=[C:8]2[C:13]([CH:14]=[C:6]([CH2:4][OH:3])[NH:7]2)=[CH:12][CH:11]=1
Reactant: CCOC(=O)c1cc2ccc(Cl)cc2[nH]1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: CCOCC
Product: OCc1cc2ccc(Cl)cc2[nH]1
Yield: 101 %

Procedure:
To a solution of 2.00 g (8.94 mmol) 6-chlorindole-2-carboxylic acid ethyl ester in 50 ml diethyl ether were added 0.475 g (12.5 mmol) lithium aluminum hydride at 0° C. The reaction mixture was heated at reflux for 45 min and quenched by consecutive addition of 10 ml water, 10 ml aqueous 2 M sodium hydroxide solution and 10 ml water at 0° C. The aqueous layer was extracted with tert-butyl methyl ether (3×100 ml). The combined organic layers were dried over sodium sulfate and concentrated in vacuo to give the crude title compound (1.64 g; 100%) as a white solid. MS m/e (%): 180 (M−H+, 100).
Reaction SMILES: [CH3:1][NH:2][CH3:3].ClC[CH2:6][C:7]1[CH:8]=[C:9]([C:18]([O:20][CH3:21])=[O:19])[C:10]([C:14]([O:16][CH3:17])=[O:15])=[N:11][C:12]=1Cl>CO>[C:14]([O-:16])(=[O:15])[CH3:10].[CH3:1][N:2]1[C:12]2=[N:11][C:10]([C:14]([O:16][CH3:17])=[O:15])=[C:9]([C:18]([O:20][CH3:21])=[O:19])[CH:8]=[C:7]2[CH2:6][CH2:3]1
Reactant: CNC
Reactant: COC(=O)c1cc(CCCl)c(Cl)nc1C(=O)OC
Solvent: CO
Product: CC(=O)[O-]
Product: COC(=O)c1cc2c(nc1C(=O)OC)N(C)CC2
Temperature: 25 °C
Reaction time: 64 h
Yield: 28.1 %

Procedure:
Dimethylamine (7.5 g, 166.6 mol) is bubbled into a solution of dimethyl 5-(2-chloroethyl)-6-chloro-2,3-pyridinedicarboxylate (20.0 g, 66mmol) in methanol (400 mL) over three hours. The resulting solution is stirred for 64 hours at room temperature and then four and one-half hours at reflux. After cooling the mixture is concentrated under vacuum and the crude product chromatographed on 250 g silica using 2:1 hexanes:ethyl acetate and then 1:1 hexanesethyl acetate as eluant, affording 2.32 g (14%) of dimethyl 1-methyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine-5,6-dicarboxylate, which is recrystallized from methylene chloride/hexanes, having a melting point 132°-133° C.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[CH:8][C:9]([O:11][CH3:12])=[O:10].C(Cl)(Cl)[Cl:14]>C1COCC1.O=[Pt]=O>[ClH:14].[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[CH2:7][CH2:8][C:9]([O:11][CH3:12])=[O:10]
Reactant: COC(=O)C=Cc1ccccn1
Reactant: ClC(Cl)Cl
Agent: O=[Pt]=O
Solvent: C1CCOC1
Product: COC(=O)CCC1CCCCN1
Product: Cl
Reaction time: 8 h

Procedure:
Methyl 3-(pyridin-2-yl)acrylate (22.15 g, 136 mmol) was dissolved in THF (300 ml) and chloroform (10.9 ml), and PtO2 (3.08 g, 13.6 mmol, 0.1 eq.) was added under a nitrogen atmosphere. The solution was first rinsed with nitrogen for 10 min and was then stirred overnight under a H2 atmosphere (8 bar). After cooling, rinsing with nitrogen was first carried out again, the catalyst was removed by filtering over filtering earth and then rinsed with DCM, and the filtrate was concentrated to dryness in vacuo. The methyl 3-(piperidin-2-yl)propionate hydrochloride was used in the next stage without being purified further.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([CH2:14][CH2:15][OH:16])=[CH:10][CH:9]=2)[CH:2]=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1.[N+](=[CH:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[N-].[OH-].[Na+]>C(Cl)Cl.O>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([CH2:7][C:8]2[CH:9]=[CH:10][C:11]([CH2:14][CH2:15][O:16][CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[CH:12][CH:13]=2)[CH:2]=1
Reactant: CCOC(=O)C=[N+]=[N-]
Reactant: OCCc1ccc(Cc2cccnc2)cc1
Agent: Cc1ccc(S(=O)(=O)O)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Solvent: O
Product: CCOC(=O)COCCc1ccc(Cc2cccnc2)cc1
Yield: 15.7 %

Procedure:
In 10 ml of methylene chloride was dissolved 1.0 g of 2-[4-(pyridin-3-ylmethyl)phenyl]ethanol, and 980 mg of p-toluene sulfonic acid monohydrate was added thereto with ice-cooling. To the resulting solution was added 2.7 g of ethyl diazoacetate with ice-cooling, after which 700 mg of boron trifluoridediethyl ether complex was dropped into the solution. The resulting mixture was subjected to reaction at the same temperature for one hour. Subsequently, 20 ml of water and 20 ml of methylene chloride were added to the reaction mixture, and the pH thereof was adjusted to 8 with 1N aqueous sodium hydroxide solution, after which the organic layer was separated, washed successively with 20 ml of water and 20 ml of a saturated aqueous sodium chloride solution, and then dried over anhydrous sodium sulfate. The solvent was then removed by distillation under reduced pressure. The residue thus obtained was purified by a column chromatography [Wako Silica Gel C-200, eluent: toluene:ethyl acetate (1:1 by volume)], to obtain 220 mg (yield 15.7%) of oily ethyl 2-[4-(pyridin-3-ylmethyl)phenyl]ethyloxyacetate.