Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([N:12]1[CH2:17][CH:16]3[CH2:18][CH:13]1[CH2:14][N:15]3[CH:19]([CH3:21])[CH3:20])=[N:7][N:6]=[CH:5]2.[CH:22]1([NH:25][C:26](=[O:43])[C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[C:29](B3OC(C)(C)C(C)(C)O3)[CH:28]=2)[CH2:24][CH2:23]1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.CCO.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>[CH:22]1([NH:25][C:26](=[O:43])[C:27]2[CH:32]=[CH:31][C:30]([CH3:33])=[C:29]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8]([N:12]3[CH2:17][CH:16]5[CH2:18][CH:13]3[CH2:14][N:15]5[CH:19]([CH3:21])[CH3:20])=[N:7][N:6]=[CH:5]4)[CH:28]=2)[CH2:23][CH2:24]1
Reactant: CC(C)N1CC2CC1CN2c1nncc2cc(Br)ccc12
Reactant: Cc1ccc(C(=O)NC2CC2)cc1B1OC(C)(C)C(C)(C)O1
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: [K+]
Solvent: CCO
Solvent: COCCOC
Product: Cc1ccc(C(=O)NC2CC2)cc1-c1ccc2c(N3CC4CC3CN4C(C)C)nncc2c1
Temperature: 90 °C
Reaction time: 1 h
Yield: 78.5 %

Procedure:
A mixture of 2-(6-bromophthalazin-1-yl)-5-isopropyl-2,5-diaza-bicyclo[2.2.1]heptane (60 mg, 173 μmol), N-cyclopropyl-4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (52 mg, 173 μmol) and tetrakis(triphenylphosphine)palladium (10 mg, 9 μmol)in 5 mL DME/EtOH (4:1) was treated with 2M potassium carbonate (0.5 mL, 1 mmol) at 22° C. under nitrogen. The mixture was heated up to 90° C. and stirred for 1 h. The reaction was monitored by MS. After about 1 h at 90° C., MS showed all starting material was converted to product (M+1=442). The mixture was cooled down to room temperature (22° C.). The mixture was transferred directly to silica gel and purified via flash chromatography (silica gel) eluting with a gradient of 2% 2 M ammonia in MeOHIDCM to 6% 2 M ammonia in MeOH/DCM to give the title compound (60 mg). Found MS (ES+): 442(M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15].[C:34]([O:40][C:41]1[CH:49]=[CH:48][C:44]([C:45](Cl)=O)=[CH:43][CH:42]=1)(=[O:39])[C:35]([CH3:38])([CH3:37])[CH3:36]>>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[C:4]([CH2:45][C:44]1[CH:43]=[CH:42][C:41]([O:40][C:34](=[O:39])[C:35]([CH3:37])([CH3:36])[CH3:38])=[CH:49][CH:48]=1)=[CH:5][N:6]2[C@@H:11]1[O:28][C@H:27]([CH2:29][O:30][C:31](=[O:33])[CH3:32])[C@@H:22]([O:23][C:24](=[O:26])[CH3:25])[C@H:17]([O:18][C:19](=[O:21])[CH3:20])[C@H:12]1[O:13][C:14](=[O:16])[CH3:15]
Reactant: CC(C)(C)C(=O)Oc1ccc(C(=O)Cl)cc1
Reactant: CC(=O)OC[C@H]1O[C@@H](n2ccc3c(Cl)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O
Product: CC(=O)OC[C@H]1O[C@@H](n2cc(Cc3ccc(OC(=O)C(C)(C)C)cc3)c3c(Cl)cccc32)[C@H](OC(C)=O)[C@@H](OC(C)=O)[C@@H]1OC(C)=O

Procedure:
4-Chloro-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)-indole obtained in Example 1-(3) and 4-pivaloyloxybenzoyl chloride were treated in a manner similar to Example 2-(4), (5) and 27-(3) to give 4-chloro-3-(4-pivaloyloxyphenylmethyl)-1-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl)indole as a colorless powder. APCI-Mass m/Z 689/691 (M+NH4).
Reaction SMILES: [C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH:22]=O)[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2].[NH2:24][CH2:25][C:26]#[N:27].C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+].C([O-])(O)=O.[Na+]>ClCCCl>[C:1]([C@H:5]1[CH2:10][CH2:9][C@H:8]([O:11][C:12]2[CH:13]=[C:14]3[C:19](=[CH:20][CH:21]=2)[CH:18]=[C:17]([CH2:22][NH:27][CH2:26][C:25]#[N:24])[CH:16]=[CH:15]3)[CH2:7][CH2:6]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3cc(C=O)ccc3c2)CC1
Reactant: N#CCN
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: ClCCCl
Product: CC(C)(C)[C@H]1CC[C@H](Oc2ccc3cc(CNCC#N)ccc3c2)CC1
Temperature: 25 °C
Reaction time: 15 h

Procedure:
6-((trans)-4-tert-butylcyclohexyloxy)-2-naphthaldehyde (310 mg, 1 mmol), 2-aminoacetonitrile (112 mg, 2 mmol, 2.0 eq) and acetic acid (180 mg, 3 mmol, 3.0 eq) in DCE (10 mL) was stirred at rt for 10 min. Then NaBH(OAc)3 (636 mg, 3 mmol, 3.0 eq) was added to the mixture and the mixture was stirred at rt for 15 h. Then saturated NaHCO3 was added to the mixture until pH=8. The mixture was extracted with DCM (20 mL×3). The organic layer was concentrated and the residue was purified by silica gel column chromatography eluting with DCM/CH3OH (20/1) to give product the title compound as a colorless oil (240 mg, yield: 69%). ESI-MS (M+H+): 351.2. 1H NMR (400 MHz, CDCl3) δ: 7.70 (dd, 2H), 7.68 (s, 1H), 7.41 (dd, 1H), 7.13 (d, 2H), 4.30-4.23 (m, 1H), 4.05 (s, 2H), 3.57 (s, 2H), 2.26 (d, 2H), 1.90 (d, 2H), 1.48-1.42 (m, 2H), 1.20-1.09 (m, 3H), 0.90 (s, 9H).
Reaction SMILES: [CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][NH:22][C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2].[H-].[Na+].FC(F)(F)S(O[CH2:33][C:34]([F:37])([F:36])[F:35])(=O)=O>>[CH:1]([N:4]1[CH2:9][CH2:8][CH:7]([O:10][C:11]2[CH:19]=[CH:18][C:17]3[N:16]4[CH2:20][CH2:21][N:22]([CH2:33][C:34]([F:37])([F:36])[F:35])[C:23](=[O:24])[C:15]4=[CH:14][C:13]=3[CH:12]=2)[CH2:6][CH2:5]1)([CH3:3])[CH3:2]
Reactant: CC(C)N1CCC(Oc2ccc3c(c2)cc2n3CCNC2=O)CC1
Reactant: O=S(=O)(OCC(F)(F)F)C(F)(F)F
Agent: [H-]
Agent: [Na+]
Product: CC(C)N1CCC(Oc2ccc3c(c2)cc2n3CCN(CC(F)(F)F)C2=O)CC1
Yield: 19 %

Procedure:
The title compound was synthesized in analogy to example 17, from 8-(1-isopropyl-piperidin-4-yloxy)-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one (example 1), sodium hydride and 2,2,2-trifluoroethyl trifluoromethanesulfonate, to give the title compound as a white solid (19%).
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([CH3:11])[CH:3]=1.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:5]3[CH:6]=[CH:7][C:2]([OH:1])=[CH:3][C:4]=3[CH3:11])[C:21]=12
Reactant: Cc1cc(O)ccc1B(O)O
Reactant: CC(C)n1nc(I)c2c(N)ncnc21
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: Cc1cc(O)ccc1-c1nn(C(C)C)c2ncnc(N)c12
Temperature: 80 °C
Yield: 44.9 %

Procedure:
A solution of 4-hydroxy-2-methylphenylboronic acid (110 mg, 0.66 mmol) in EtOH (3.3 ml) was added to a solution of 3-iodo-1-isopropyl-1H-pyrazolo[3,4-d]pyrimidin-4-amine (100 mg, 0.33 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 silica gel column chromatography [MeOH—CH2Cl2, 2:98] to yield BA60 (42 mg, 22% yield). ESI-MS (M+H)+ m/z calcd 284, found 284.
Reaction SMILES: [N+:1]([O-:4])(O)=[O:2].[CH3:5][O:6][C:7]1[CH:8]=[C:9]([CH:33]=[CH:34][C:35]=1[O:36][CH3:37])[C:10]([C:12]1[C:13]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:14][N:15]([CH:17]([O:21][C:22]([O:24][CH:25]([CH3:27])[CH3:26])=[O:23])[CH:18]([CH3:20])[CH3:19])[N:16]=1)=[O:11]>>[CH3:37][O:36][C:35]1[C:7]([O:6][CH3:5])=[CH:8][C:9]([C:10]([C:12]2[C:13]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:14][N:15]([CH:17]([O:21][C:22]([O:24][CH:25]([CH3:26])[CH3:27])=[O:23])[CH:18]([CH3:20])[CH3:19])[N:16]=2)=[O:11])=[C:33]([N+:1]([O-:4])=[O:2])[CH:34]=1
Reactant: O=[N+]([O-])O
Reactant: CCOC(=O)c1nn(C(OC(=O)OC(C)C)C(C)C)nc1C(=O)c1ccc(OC)c(OC)c1
Product: CCOC(=O)c1nn(C(OC(=O)OC(C)C)C(C)C)nc1C(=O)c1cc(OC)c(OC)cc1[N+](=O)[O-]
Reaction time: 0.5 h

Procedure:
70% nitric acid (1 ml) was added to ethyl 5-(3,4-dimethoxybenzoyl)-2-(1-isopropoxycarbonyloxy-2-methylpropyl)-2H-1,2,3-triazole-4-carboxylate (86 mg, 0.19 mmol) as Intermediate 8 under ice cooling. The mixture was stirred at that temperature for 30 min. The reaction solution was poured into ice and then extracted with ethyl acetate. The organic layer was washed with a saturated aqueous sodium hydrogencarbonate solution and saturated brine solution in that order and dried over anhydrous magnesium sulfate. The solvent was evaporated to give the title compound as a single compound (49 mg, 52%). The Rf value of thin-layer chromatography on silica gel and 1H-NMR spectrum were the same as those of the title compound of Example 20 (a).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:22](=[O:23])[N:21]([CH2:24][CH3:25])[C:14]3[N:15]=[C:16](SC)[N:17]=[N:18][C:13]=3[CH:12]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1.[NH2:26][C:27]1[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=1>>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:11]2[C:22](=[O:23])[N:21]([CH2:24][CH3:25])[C:14]3[N:15]=[C:16]([NH:26][C:27]4[CH:32]=[CH:31][N:30]=[CH:29][CH:28]=4)[N:17]=[N:18][C:13]=3[CH:12]=2)[CH:6]=[C:7]([O:9][CH3:10])[CH:8]=1
Reactant: CCn1c(=O)c(-c2cc(OC)cc(OC)c2)cc2nnc(SC)nc21
Reactant: Nc1ccncc1
Product: CCn1c(=O)c(-c2cc(OC)cc(OC)c2)cc2nnc(Nc3ccncc3)nc21
Reaction time: 144 h
Yield: 30.2 %

Procedure:
A homogenious mixture of 1.8 g (5.0 mmol) of 7-(3,5-dimethoxy-phenyl)-5-ethyl-3-methylsulfanyl-5H-pyrido[2,3-e]-1,2,4-triazin-6-one and 3.3 g (35.2 mmol) of 4-aminopyridine was heated at 150° C. for 2 days in a sealed reaction vessel, during which time the sublimed 4-aminopyrdine was reintroduced to the reaction mixture. At the end of 2 days, the sublimed 4-aminopyridine was removed, and the remaining mixture was triturated under 1:9 methanol/chloroform at room temperature and filtered. The solid was suspended in 60 mL of hot chloroform while methanol was added to produce a near homogeneous solution that was filtered and set aside for 6 days. The crystals were collected, washed with chloroform, and dried under house vacuum to give 610 mg (30%) of the title compound as yellow platelets. Mp=316-318° C. (dec).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:12][CH2:11][C:10](=O)[CH2:9]2)=[CH:4][CH:3]=1.CO.C([O-])(=O)C.[Na+].Cl.[NH2:22][OH:23]>CC(OC)(C)C>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]2[CH2:12][CH2:11][C:10](=[N:22][OH:23])[CH2:9]2)=[CH:4][CH:3]=1
Reactant: NO
Reactant: O=C1CC[C@H](c2ccc(Br)cc2)C1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: COC(C)(C)C
Solvent: CO
Product: ON=C1CC[C@H](c2ccc(Br)cc2)C1
Reaction time: 0.17 h
Yield: 95.2 %

Procedure:
A slurry of (S)-3-(4-bromophenyl)cyclopentanone (prepared according to J. Org. Chem., 2009, 74, 929; 10.9 g, 45.5 mmol), MeOH (110 mL), sodium acetate (5.59 g, 68.2 mmol), and hydroxylamine hydrochloride (4.74 g, 68.2 mmol) was stirred at room temperature. After 10 minutes, LCMS showed complete reaction. Diluted with MTBE (300 mL) and washed with water (100 mL) and brine (50 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by silica gel chromatography (gradient elution, 25-50% EtOAc/hexanes) to afford the title compound (11.0 g, 43.3 mmol, 95%). MS (DCI) m/z 254 (M+H)+.
Reaction SMILES: [CH3:1][N:2]([CH3:14])[C:3]1[CH:11]=[C:10]([CH3:12])[C:6]([C:7](O)=[O:8])=[C:5]([F:13])[CH:4]=1.C(N1C=CN=C1)([N:17]1C=CN=C1)=O>C1COCC1>[CH3:1][N:2]([CH3:14])[C:3]1[CH:11]=[C:10]([CH3:12])[C:6]([C:7]([NH2:17])=[O:8])=[C:5]([F:13])[CH:4]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: Cc1cc(N(C)C)cc(F)c1C(=O)O
Solvent: C1CCOC1
Product: Cc1cc(N(C)C)cc(F)c1C(N)=O
Reaction time: 0.5 h
Yield: 78.1 %

Procedure:
To a suspension of 4-Dimethylamino-2-fluoro-6-methyl-benzoic acid (0.896 g, 4.54 mmol) in THF (11 mL) was added carbonyldiimidazole (0.958 g, 5.91 mmol). The solution became homogeneous with bubbling. After 30 min., this solution was added to concentrated ammonium hydroxide (7 mL), and the solution became cloudy. Following removal of solvent after 1 h, the residue was taken up in H2O and filtered to give 4-dimethylamino-2-fluoro-6-methyl-benzamide as a white solid (0.696 g, 78%).
Reaction SMILES: [C:1]([O-:4])(=[S:3])[CH3:2].[K+].[CH2:6]([O:9][C:10]([N:12]1[C@H:16]([CH:17]([OH:26])[C:18]2[S:22][C:21]3=[CH:23][N:24]=[CH:25][N:20]3[CH:19]=2)[CH2:15][C@@H:14](OS(C)(=O)=O)[CH2:13]1)=[O:11])[CH:7]=[CH2:8].O>CN(C=O)C>[C:1]([S:3][C@H:14]1[CH2:15][C@@H:16]([CH:17]([OH:26])[C:18]2[S:22][C:21]3=[CH:23][N:24]=[CH:25][N:20]3[CH:19]=2)[N:12]([C:10]([O:9][CH2:6][CH:7]=[CH2:8])=[O:11])[CH2:13]1)(=[O:4])[CH3:2]
Reactant: CC([O-])=S
Reactant: C=CCOC(=O)N1C[C@H](OS(C)(=O)=O)C[C@H]1C(O)c1cn2cncc2s1
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: C=CCOC(=O)N1C[C@@H](SC(C)=O)C[C@H]1C(O)c1cn2cncc2s1
Reaction time: 5 h
Yield: 60.6 %

Procedure:
Potassium thioacetate (204 mg) is added to a solution of 236.9 mg of (3R,5S)-1-allyloxycarbonyl-3-methanesulfonyloxy-5-[1-hydroxy-1-(imidazo[5,1-b]thiazol-2-yl)methyl]pyrrolidine (a diastereomer mixture) in 10 ml of DMF, and the mixture is stirred under an argon stream a 70° C. for 5 hr. The reaction solution is cooled, water is added thereto, and the mixture is extracted three times with ethyl acetate. The organic layer is washed once with saturated saline, dried over anhydrous magnesium sulfate and filtered, and the solvent is removed by evaporation under reduced pressure. The resultant crude product is purified by column chromatography on silica gel (hexane:acetone=1:1) to give 136.4 mg of the title compound (a diastereomer mixture) as a brown oil.
Reaction SMILES: C1(C(SC[CH2:10][C:11]([NH:13][CH2:14][C:15](O)=O)=[O:12])=O)SC=CC=1.O1[CH2:22][CH2:21][CH2:20][CH2:19]1.C(OC(Cl)=O)C>C(Cl)Cl>[C:11]([NH:13][C:14]1[CH:15]=[CH:22][CH:21]=[CH:20][CH:19]=1)(=[O:12])[CH3:10]
Reactant: O=C(O)CNC(=O)CCSC(=O)c1cccs1
Reactant: C1CCOC1
Agent: CCOC(=O)Cl
Solvent: ClCCl
Product: CC(=O)Nc1ccccc1

Procedure:
5.4 grams (0.020 moles) of 2-thenoylmercaptopropionylglycine were added to 50 ml of tetrahydrofurane. The temperature of the resulting mixture was brought to 0° C., then a solution of ethylchloroformate (2.2 grams; 0.020 moles) in 10 ml of anhydrous CH2Cl2 was slowly added. To the resulting solution, the following solution was slowly added:
Reaction SMILES: [CH3:1][C:2]1[O:6][N:5]=[C:4]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][N:8]=2)[C:3]=1[CH2:13][O:14][C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][N:16]=1.[CH2:24]([NH2:26])[CH3:25]>>[CH2:24]([NH:26][C:19](=[O:21])[C:18]1[CH:22]=[CH:23][C:15]([O:14][CH2:13][C:3]2[C:4]([C:7]3[CH:12]=[CH:11][N:10]=[CH:9][N:8]=3)=[N:5][O:6][C:2]=2[CH3:1])=[N:16][CH:17]=1)[CH3:25]
Reactant: CCN
Reactant: Cc1onc(-c2ccncn2)c1COc1ccc(C(=O)O)cn1
Product: CCNC(=O)c1ccc(OCc2c(-c3ccncn3)noc2C)nc1
Yield: 78 %

Procedure:
As described for example 313b, 6-(5-methyl-3-pyrimidin-4-yl-isoxazol-4-ylmethoxy)-nicotinic acid (53 mg, 0.17 mmol) was converted, using ethylamine (2 M solution in THF) instead of isopropylamine, to the title compound (45 mg, 78%) which was obtained as a white solid. MS: m/e=340.0 [M+H]+.
Reaction SMILES: N([O-])=O.[Na+].[CH3:5][S:6][C:7]1[S:8][C:9]([C:13]#[N:14])=[C:10](N)[N:11]=1.Cl.C(Cl)[Cl:17]>O>[CH3:5][S:6][C:7]1[S:8][C:9]([C:13]#[N:14])=[C:10]([Cl:17])[N:11]=1
Reactant: ClCCl
Reactant: CSc1nc(N)c(C#N)s1
Agent: Cl
Agent: O=N[O-]
Agent: [Na+]
Solvent: O
Product: CSc1nc(Cl)c(C#N)s1
Temperature: 0 °C

Procedure:
A concentrated solution of 42 g of sodium nitrite in water is slowly added dropwise to a mixture of 68.4 g of 2-methylthio-4-amino-5-cyanothiazole, obtained according to example III, 100 ml of water, 300 ml of concentrated hydrochloric acid, 70 g of cuprous chloride (CuCl2.2H2O) and 800 ml of methylene chloride while stirring and cooling at approximately 0° C. After stirring for another 30 minutes at 0°-5° C. the mixture is diluted with water. The reaction mixture is filtered off and the filtrate is separated; the organic layer is washed with water, dried, filtered and evaporated while adding isopropanol until crystallisation. The desired compound is obtained in a yield of 46.3 g; m.p. 83°-87° C.
Reaction SMILES: [C:1]1([C:7]([CH:9]([C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)[OH:10])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[N:17]([CH2:20][C:21]1([CH2:27][C:28]([O:30][CH2:31][CH2:32][C:33]#[N:34])=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)=[C:18]=[O:19]>C1(C)C=CC=CC=1>[C:7]([CH:9]([O:10][C:18]([NH:17][CH2:20][C:21]1([CH2:27][C:28]([O:30][CH2:31][CH2:32][C:33]#[N:34])=[O:29])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)=[O:19])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)(=[O:8])[C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: N#CCCOC(=O)CC1(CN=C=O)CCCCC1
Reactant: O=C(c1ccccc1)C(O)c1ccccc1
Solvent: Cc1ccccc1
Product: N#CCCOC(=O)CC1(CNC(=O)OC(C(=O)c2ccccc2)c2ccccc2)CCCCC1
Yield: 83 %

Procedure:
A solution of benzoin (0.599 mmol) and 2-cyanoethyl 1-isocyanatomethyl-1-cyclohexane acetate (7) (0.599 mmol) in 10 mL of anhydrous toluene was refluxed overnight. The reaction mixture was concentrated and the residue purified on silica gel (40% ethyl acetate in hexane) to afford 230 mg (83%) of the title compound. 1H NMR (CDCl3): δ 7.95 (2H, dd, J=8.2, 1.4 Hz); 7.50-7.46 (3H, m); 7.41 (5H, m); 6.84 (1H, s); 5.40 (1H, t, J=6.8 Hz); 4.26 (2H, m); 3.24 (2H, d, J=6.8 Hz); 2.68 (2H, dt, J=2.4, 6.4 Hz); 2.36 (2H, d, J=1.2 Hz); 1.52-1.37 (10H, m).
Reaction SMILES: [C:1]1([CH2:17][CH2:18][CH2:19][CH2:20][OH:21])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1.[Cr](Cl)([O-])(=O)=O.[NH+]1C=CC=CC=1>C(Cl)Cl.CCOCC>[C:1]1([CH2:17][CH2:18][CH2:19][CH:20]=[O:21])[C:14]2[C:15]3=[C:16]4[C:11](=[CH:12][CH:13]=2)[CH:10]=[CH:9][CH:8]=[C:7]4[CH:6]=[CH:5][C:4]3=[CH:3][CH:2]=1
Reactant: OCCCCc1ccc2ccc3cccc4ccc1c2c34
Agent: O=[Cr](=O)([O-])Cl
Agent: c1cc[nH+]cc1
Solvent: CCOCC
Solvent: ClCCl
Product: O=CCCCc1ccc2ccc3cccc4ccc1c2c34
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
10 mL of methylene chloride was added to 1.097 g (4 mmol) of 4-(pyren-1-yl) butyl alcohol and stirred vigorously at room temperature for 10 min hour. The reaction was followed by addition of 1.292 g (1.5 Eq.) of PCC (Pyridinium chlorochromate) in 10 mL methylene chloride and the reaction mixture was stirred for 2 h. The reaction mixture was then diluted with 5 volumes of anhydrous ether (100 mL) and washed with 1:1 brine:water, saturated aq. Na2SO3 solution, and brine, respectively, dried over anhydrous Na2SO4 and concentrated to give the aldehyde. The crude product was purified by silica gel flash chromatography (hexanes: ethyl acetate, 9:1, rf: 0.4) to yield 1.06 g (97%). Most of the crude products were very clean and could be used directly for further applications.
Reaction SMILES: [N+:1]([C:4]1[N:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][C:12](=[O:16])[CH2:11]2)=[CH:6][CH:5]=1)([O-])=O.[H][H]>[Pd].CO>[NH2:1][C:4]1[N:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][NH:13][C:12](=[O:16])[CH2:11]2)=[CH:6][CH:5]=1
Reactant: [H][H]
Reactant: O=C1CN(c2ccc([N+](=O)[O-])nc2)CCN1
Agent: [Pd]
Solvent: CO
Product: Nc1ccc(N2CCNC(=O)C2)cn1
Reaction time: 4 h

Procedure:
To a round-bottom flask was added 4-(6-nitropyridin-3-yl)piperazin-2-one 141-3 (0.7 g, 3.1 mmol), Pd/C (0.2 g) and methanol (20 mL). The reaction was stirred for 4 hours under hydrogen atmosphere by attaching a hydrogen balloon. The reaction was flashed with nitrogen and the solid was removed by filtration. The solvent was removed by rotary evaporation to give 4-(6-aminopyridin-3-yl)piperazin-2-one 141-4 as purple solid. MS m/z 193.2 (M+1).
Reaction SMILES: C(OC([NH:6][C:7]1[CH2:11][CH2:10][CH2:9][C:8]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13])=O)C.C[O-].[Na+].CO>O>[NH2:6][C:7]1[CH2:11][CH2:10][CH2:9][C:8]=1[C:12]([O:14][CH2:15][CH3:16])=[O:13]
Reactant: CCOC(=O)NC1=C(C(=O)OCC)CCC1
Agent: C[O-]
Agent: [Na+]
Solvent: O
Solvent: CO
Product: CCOC(=O)C1=C(N)CCC1
Temperature: 25 °C
Yield: 88.2 %

Procedure:
A solution containing ethyl 2-[(ethoxycarbonyl)-amino]-1-cyclopentene-1-carboxylate (72 g, 0.32 moles) and 25 wt % sodium methoxide in methanol (91.5 mL, 0.40 moles) was refluxed for about 18 hours. Methanol (200 mL) was added during the course of the reaction. The reaction mixture was allowed to cool to ambient temperature then diluted with water and extracted with diethyl ether (5×100 mL). The ether extracts were combined, treated with activated charcoal, dried over sodium sulfate then evaporated to provide 43.8 g of ethyl 2-amino-1-cyclopentene-1-carboxylate as an ivory solid, m.p. 90°-92° C.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:14][CH3:15])=[C:9]([O:12][CH3:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[I:16][C:17]1[CH:24]=[C:21]([CH:22]=[O:23])[C:20]([OH:25])=[CH:19][CH:18]=1.O>CN(C)C1C=CN=CC=1.ClC1C=CC=CC=1>[CH3:13][O:12][C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][C:8]=1[O:14][CH3:15])[N:5]=[CH:4][CH:3]=[C:2]2[O:25][C:20]1[CH:19]=[CH:18][C:17]([I:16])=[CH:24][C:21]=1[CH:22]=[O:23]
Reactant: COc1cc2nccc(Cl)c2cc1OC
Reactant: O=Cc1cc(I)ccc1O
Agent: CN(C)c1ccncc1
Solvent: O
Solvent: Clc1ccccc1
Product: COc1cc2nccc(Oc3ccc(I)cc3C=O)c2cc1OC
Temperature: 130 °C
Reaction time: 8 h

Procedure:
4-Chloro-6,7-dimethoxyquinoline (111 mg), 5-iodosalicylaldehyde (496 mg), and 4-dimethylaminopyridine (244 mg) were suspended in monochlorobenzene (2 ml), and the mixture was stirred at 130° C. overnight. The reaction solution was cooled to room temperature, water was then added to the reaction solution, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was then washed with water and saturated brine and was dried over anhydrous sodium sulfate. The solvent was removed therefrom by distillation under the reduced pressure, and the residue was purified by chromatography on silica gel using ethyl acetate-hexane for development to give 2-[(6,7-dimethoxy-4-quinolyl)oxy]-5-iodobenzaldehyde.
Reaction SMILES: [CH3:1][N:2]1[C:6]([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=O)=[N:5][CH:4]=[N:3]1.Cl.[NH2:16][OH:17]>N1C=CC=CC=1>[OH:17]/[N:16]=[C:7](\[C:6]1[N:2]([CH3:1])[N:3]=[CH:4][N:5]=1)/[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: NO
Reactant: Cn1ncnc1C(=O)c1ccccc1
Agent: Cl
Solvent: c1ccncc1
Product: Cn1ncnc1/C(=N\O)c1ccccc1
Temperature: 50 °C
Reaction time: 8 h
Yield: 88.9 %

Procedure:
To a solution of (1-methyl-1H-1,2,4-triazol-5-yl)(phenyl)methanone (5.5 g, 29.38 mmol, 1 eq.) in 100 ml of pyridine was added hydroxylamine hydrochloride (5.1 g, 73.45 mmol, 2.5 eq.). The temperature was raised to 50° C. and the reaction stirred overnight. The solvent was then evaporated and the residue dissolved in DCM and washed with H2O. The organic layer was washed with 0.1N HCl and dried over MgSO4. The solvent was evaporated to give ((Z)-N-hydroxy-1-(1-methyl-1H-1,2,4-triazol-5-yl)-1-phenylmethanimine (5.28 g, 89% yield) as a white solid.