Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(O[C:4](=[O:24])[CH:5]=[C:6]([NH:8][C:9]1[CH:14]=[CH:13][C:12]([Br:15])=[C:11]([O:16][CH2:17][C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=1)[CH3:7])C>C1C=CC(C2C=CC=CC=2)=CC=1.C1C=CC(OC2C=CC=CC=2)=CC=1>[CH2:17]([O:16][C:11]1[CH:10]=[C:9]2[C:14]([C:4]([OH:24])=[CH:5][C:6]([CH3:7])=[N:8]2)=[CH:13][C:12]=1[Br:15])[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=1
Reactant: CCOC(=O)C=C(C)Nc1ccc(Br)c(OCc2ccccc2)c1
Solvent: c1ccc(-c2ccccc2)cc1
Solvent: c1ccc(Oc2ccccc2)cc1
Product: Cc1cc(O)c2cc(Br)c(OCc3ccccc3)cc2n1
Temperature: 250 °C
Yield: 213.2 %

Procedure:
Dowtherm®A (320 mL) was heated to 250° C. then a solution of 3-(3-benzyloxy-4-bromo-phenylamino)-but-2-enoic acid ethyl ester (55.5 g, 99.5 mmol) in Dowtherm®A (120 mL) was slowly added. The reaction mixture was heated 16 min at 250° C. and ethanol was collected by distillation. The mixture was cooled down, diluted with hexanes (1.5 L) and filtered. The solid was washed with ether and dried under vacuum. 73.0 g of the title compound were obtained. Brown solid, ISP-MS: m/e=345.2 ([M+H]+).
Reaction SMILES: N#N.[C:3]1([C:9]2[O:13][CH:12]=[N:11][C:10]=2[C:14]([OH:16])=O)[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl.CCN(C(C)C)C(C)C.[CH3:40][O:41][CH2:42][C:43]1[O:47][C:46]([CH2:48][N:49]2[N:53]=[C:52]([NH2:54])[CH:51]=[N:50]2)=[CH:45][CH:44]=1>C(Cl)Cl.CN(C1C=CN=CC=1)C>[CH3:40][O:41][CH2:42][C:43]1[O:47][C:46]([CH2:48][N:49]2[N:53]=[C:52]([NH:54][C:14]([C:10]3[N:11]=[CH:12][O:13][C:9]=3[C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=3)=[O:16])[CH:51]=[N:50]2)=[CH:45][CH:44]=1
Reactant: O=C(O)c1ncoc1-c1ccccc1
Reactant: COCc1ccc(Cn2ncc(N)n2)o1
Agent: CN(C)c1ccncc1
Agent: N#N
Agent: On1nnc2ccccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: ClCCCl
Product: COCc1ccc(Cn2ncc(NC(=O)c3ncoc3-c3ccccc3)n2)o1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), a solution of commercially available 5-phenyloxazole-4-carboxylic acid (52 mg, 0.26 mmol) in CH2Cl2 (3.0 mL) was treated at rt with DMAP (8.1 mg, 0.07 mmol), HOBt (42.8 mg, 0.32 mmol), EDC (127 mg, 0.66 mmol) and DIPEA (0.2 mL, 1.17 mmol) and the resulting mixture was stirred for 30 min at rt. A solution of 2-((5-(methoxymethyl)furan-2-yl)methyl)-2H-1,2,3-triazol-4-amine (55 mg, 0.26 mmol) in CH2Cl2 (3.0 mL) was then added and the reaction mixture was stirred overnight at rt. The mixture was diluted with CH2Cl2 (10.0 mL), the layers were separated and the org. phase was washed with water (10.0 mL), followed by brine (10.0 mL) and dried over MgSO4, filtered and the solvents were removed under reduced pressure. Purification of the residue by FC (6:4 hept-EA) gave the title compound as a colorless oil: TLC: rf (6:4 hept-EA)=0.23. LC-MS-conditions 07: tR=0.87 min, [M+H]+=380.26
Reaction SMILES: [N:1]1([CH2:6][CH2:7][CH2:8][NH2:9])[CH:5]=[CH:4][N:3]=[CH:2]1.[CH2:10]([O:12][C:13]([C:15]1[C:16](=[O:38])[C:17]2[CH:22]=[N:21][C:20](S(C)(=O)=O)=[N:19][C:18]=2[N:27]([C:29]2[CH:30]=[C:31]3[C:35](=[CH:36][CH:37]=2)[CH2:34][CH2:33][CH2:32]3)[CH:28]=1)=[O:14])[CH3:11]>>[CH2:10]([O:12][C:13]([C:15]1[C:16](=[O:38])[C:17]2[CH:22]=[N:21][C:20]([NH:9][CH2:8][CH2:7][CH2:6][N:1]3[CH:5]=[CH:4][N:3]=[CH:2]3)=[N:19][C:18]=2[N:27]([C:29]2[CH:30]=[C:31]3[C:35](=[CH:36][CH:37]=2)[CH2:34][CH2:33][CH2:32]3)[CH:28]=1)=[O:14])[CH3:11]
Reactant: CCOC(=O)c1cn(-c2ccc3c(c2)CCC3)c2nc(S(C)(=O)=O)ncc2c1=O
Reactant: NCCCn1ccnc1
Product: CCOC(=O)c1cn(-c2ccc3c(c2)CCC3)c2nc(NCCCn3ccnc3)ncc2c1=O

Procedure:
Using the procedure outlined in Example 1(Step F) the title compound was prepared from 3-imidazol-1-yl-propylamine (4.4 μL, 0.036 mmol) and 8-indan-5-yl-2-methanesulfonyl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester (from Example 1(Step E), 15 mg, 0.036 mmol). 19.2 mg of 2-(3-imidazol-1-yl-propylamino)-8-indan-5-yl-5-oxo-5,8-dihydro-pyrido[2,3-d]pyrimidine-6-carboxylic acid ethyl ester was obtained as a white solid. 1H NMR (300 MHz, CDCl3) δ (ppm): 9.22 (s, 1H), 8.45 (s, 1H), 7.50 (br, 1H), 7.32 (d, 1H), 7.22 (s, 1H), 7.15 (d, 1H), 7.03 (br, 1H), 6.78 (br, 1H), 6.10 (br, 1H), 4.36 (q, 2H), 3.75 (m, 2H), 3.10 (m, 2H), 2.97 (m, 4H), 2.14 (m, 2H), 1.92 (m, 2H), 1.40 (t, 3H). Mass Spectrum (LCMS, ESI pos.) Calcd. For C25H26N6O3: 459.21 (M+H). Found: 459.4.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH2:9])=[N:4][C:5]([NH2:8])=[CH:6][CH:7]=1.C(N(CC)CC)C.C1COCC1.[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[CH:28][C:24]=1[C:25](Cl)=[O:26]>C(Cl)Cl>[NH2:9][C:3]1[N:4]=[C:5]([NH:8][C:25]([C:24]2[CH:28]=[CH:29][CH:30]=[CH:31][C:23]=2[F:22])=[O:26])[CH:6]=[CH:7][C:2]=1[Br:1]
Reactant: O=C(Cl)c1ccccc1F
Reactant: Nc1ccc(Br)c(N)n1
Solvent: CCN(CC)CC
Solvent: ClCCl
Solvent: C1CCOC1
Product: Nc1nc(NC(=O)c2ccccc2F)ccc1Br
Temperature: -78 °C
Reaction time: 1 h
Yield: 57 %

Procedure:
A solution of 3-bromo-2,6-diaminopyridine (60) (564 mg, 3 mmol), triethyl amine (0.54 ml) in DCM (6 ml)/THF (4 ml) was cooled down to −78° C. A solution of 2-fluorobenzoyl chloride (362 μl, 3.03 mmol) in 2 ml DCM was added dropwise within 10 min. The resulting reaction mixture was stirred at −78° C. for 1 h before slowly warm up to r.t. After stirred at r.t. for 3 h, the reaction quenched with aq NaHCO3 solution. 200 ml EA were added. Org. phase was washed with brine, dried over sodium sulfate, concentrated. The light yellow solid residue was triturated with DCM (ca. 15 ml), filtered and dried to give 530 mg N-(6-amino-5-bromo(2-pyridyl))(2-fluorophenyl)carboxamide (61) as white solid. (purity>95%, yield: 57%).
Reaction SMILES: O.[CH3:2][C:3]1([CH3:12])[CH2:8][C:7](=[O:9])[CH2:6][C:5]([CH3:11])([CH3:10])[NH:4]1.[C:13]([CH2:15][CH2:16][PH:17](=[O:22])[CH2:18][CH2:19][C:20]#[N:21])#[N:14]>C(N(CC)CC)C.C(O)(C)C>[CH3:2][C:3]1([CH3:12])[CH2:8][C:7]([P:17](=[O:22])([CH2:18][CH2:19][C:20]#[N:21])[CH2:16][CH2:15][C:13]#[N:14])([OH:9])[CH2:6][C:5]([CH3:11])([CH3:10])[NH:4]1
Reactant: CC1(C)CC(=O)CC(C)(C)N1
Reactant: N#CCC[PH](=O)CCC#N
Solvent: CCN(CC)CC
Solvent: CC(C)O
Solvent: O
Product: CC1(C)CC(O)(P(=O)(CCC#N)CCC#N)CC(C)(C)N1
Yield: 64.2 %

Procedure:
To 100 milliliters of isopropanol was added 8.65 grams (0.05 mole) of 2,2,6,6-tetramethyl-4-piperidone hydrate; 7.81 grams (0.05 mole) of bis(2-cyanoethyl)phosphine oxide; and 1 gram of triethylamine as catalyst. The reaction mixture was refluxed four hours, cooled in an ice bath, and the crystalline product filtered off. After recrystallization, there was obtained 10.0 grams of white crystalline product of 128°-130°C. melting point, representing a 65% yield.
Reaction SMILES: [N+:1]([C:4]1[CH:26]=[CH:25][C:7]([C:8]([C:10]2[CH:15]=[C:14]([C:16]([CH3:19])([CH3:18])[CH3:17])[C:13]([OH:20])=[C:12]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:11]=2)=[O:9])=[CH:6][CH:5]=1)([O-])=O.[NH4+]=S>C(O)C>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([C:8]([C:10]2[CH:15]=[C:14]([C:16]([CH3:18])([CH3:19])[CH3:17])[C:13]([OH:20])=[C:12]([C:21]([CH3:24])([CH3:23])[CH3:22])[CH:11]=2)=[O:9])=[CH:25][CH:26]=1
Reactant: CC(C)(C)c1cc(C(=O)c2ccc([N+](=O)[O-])cc2)cc(C(C)(C)C)c1O
Solvent: CCO
Product: CC(C)(C)c1cc(C(=O)c2ccc(N)cc2)cc(C(C)(C)C)c1O

Procedure:
A solution of 5 g. of 4-(4-nitrobenzoyl)-2,6-di(t-butyl)phenol in 150 ml. of ethanol is treated with 40 ml. of ammonium sulfide solution. The mixture is heated at reflux for 2 hours then stirred without heating for about 16 hours. An additional 40 ml. of ammonium sulfide solution is added, and the mixture is heated at reflux for 4 hours more. After an additional 16 hours without heating, the mixture is extracted with dichloromethane, and the extracts are dried. Evaporation of the dried extracts provides a solid residue which is recrystallized twice from a benzene-hexane mixture to provide 4-(4-aminobenzoyl)-2,6-di(t-butyl)phenol as a light yellow solid, m.p. 164.5°-166.5° C.
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[C:5]([C:10]([OH:12])=O)[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.C(Cl)(=O)C([Cl:16])=O.CCCCCC>C(Cl)Cl>[NH:1]1[C:9]2[C:4](=[C:5]([C:10]([Cl:16])=[O:12])[CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1
Reactant: O=C(O)c1cccc2[nH]ccc12
Reactant: O=C(Cl)C(=O)Cl
Solvent: CCCCCC
Solvent: ClCCl
Product: O=C(Cl)c1cccc2[nH]ccc12
Temperature: 20 °C
Reaction time: 2 h

Procedure:
32.2 g (0.2M) dry indol-4-yl carboxylic acid are suspended in 150 ml absolute methylene chloride. 26 ml (0.3M) oxalyl chloride are added to the stirred mixture at 20° over 30 minutes. Gas evolution results. The mixture is stirred for 31/2 hours at 20° C. 150 ml Hexane are added. The mixture is stirred for another 20 minutes and the resultant heading compound filtered off, washed with methylene chloride/hexane 1:1 dried at 20° in a vacuum to give beige crystals, which are used further without purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([CH3:11])([CH3:10])[CH3:9])[CH:5]=[C:4]([CH3:12])[N:3]=1.[Br:13]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl.CC(N=NC(C#N)(C)C)(C#N)C>[Br:13][CH2:12][C:4]1[CH:5]=[C:6]([C:8]([CH3:9])([CH3:11])[CH3:10])[CH:7]=[C:2]([Cl:1])[N:3]=1
Reactant: Cc1cc(C(C)(C)C)cc(Cl)n1
Reactant: O=C1CCC(=O)N1Br
Agent: CC(C)(C#N)N=NC(C)(C)C#N
Solvent: ClC(Cl)(Cl)Cl
Product: CC(C)(C)c1cc(Cl)nc(CBr)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 44.3 %

Procedure:
Dissolve 2-chloro-6-methyl-4-tert-butyl-pyridine (3.00 g, 16.33 mmol), N-bromosuccinimide (3.20 g, 17.97 mmol) and AIBN (0.03 g, 0.16 mmol) in carbon tetrachloride (60 mL) and heat to reflux. After heating for 6 hours, stir the contents overnight at ambient temperature. The contents are then concentrated to dryness and dry loaded onto a silica plug and eluted with dichloromethane to obtain the title compound (1.90 g, 7.23 mmol). MS(ES), m/z 263 (M+1).
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:17]([NH2:19])=[O:18])=[CH:4][C:5]2[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[N:7]([CH2:14][CH3:15])[C:6]=2[N:16]=1.C=O.[C:22](O)(=O)C.C([BH3-])#N.[Na+]>CO>[CH2:14]([N:7]1[C:8]2[C:13](=[CH:12][CH:11]=[CH:10][CH:9]=2)[C:5]2[CH:4]=[C:3]([C:17]([NH2:19])=[O:18])[C:2]([NH:1][CH3:22])=[N:16][C:6]1=2)[CH3:15]
Reactant: CCn1c2ccccc2c2cc(C(N)=O)c(N)nc21
Reactant: CC(=O)O
Agent: C=O
Agent: [BH3-]C#N
Agent: [Na+]
Solvent: CO
Product: CCn1c2ccccc2c2cc(C(N)=O)c(NC)nc21
Temperature: 25 °C
Reaction time: 16 h
Yield: 66.1 %

Procedure:
2-amino-9-ethyl-9H-pyrido[2,3-b]indole-3-carboxamide (1, 36 mg, 0.141 mmol), formaldehyde (37 wt % in water, 0.011 mL, 0.155 mmol) and acetic acid (0.0084 mL, 0.148 mmol) in methanol (2.6 mL) were stirred at room temperature for 1 h then sodium cyanoborohydride (13 mg, 0.212 mmol) was added. The reaction stirred at room temperature for 16 h, then was quenched with aqueous saturated sodium bicarbonate (2.6 mL). The resulting mixture was diluted with ethyl acetate (100 mL), washed with water (2×50 mL) and brine (50 mL), dried over magnesium sulfate, filtered and then concentrated in vacuo. The residue was adsorbed onto silica gel using methanol and purified by silica gel chromatography (5-10% methanol in methylene chloride gradient) to afford the title compound (48, 25 mg, 66%). NH4OAc standard conditions. DAD Retention time=7.84 min. M+H=269. 1H NMR (300 MHz, CDCl3): δ 8.60 (br s, 1H), 8.19 (s, 1H), 7.79 (d, J=7.9 Hz, 1H), 7.36-7.32 (m, 2H), 7.21-7.17 (m, 1H), 5.65 (br s, 2H), 4.38 (q, J=7.3 Hz, 2H), 3.12 (s, 3H), 1.42 (t, J=7.3 Hz, 3H).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([N:9]2[C:13]3[C:14](=[O:18])[NH:15][CH2:16][CH2:17][C:12]=3[C:11]([C:19]#[N:20])=[N:10]2)=[CH:5][CH:4]=1.I[C:22]1[CH:27]=[CH:26][C:25]([C:28]([CH3:37])([CH3:36])[CH2:29][N:30]2[CH2:34][CH2:33][CH2:32][C:31]2=[O:35])=[CH:24][CH:23]=1.C([O-])([O-])=O.[K+].[K+]>[Cu]I>[CH3:37][C:28]([C:25]1[CH:24]=[CH:23][C:22]([N:15]2[CH2:16][CH2:17][C:12]3[C:11]([C:19]#[N:20])=[N:10][N:9]([C:6]4[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:8][CH:7]=4)[C:13]=3[C:14]2=[O:18])=[CH:27][CH:26]=1)([CH3:36])[CH2:29][N:30]1[CH2:34][CH2:33][CH2:32][C:31]1=[O:35]
Reactant: CC(C)(CN1CCCC1=O)c1ccc(I)cc1
Reactant: COc1ccc(-n2nc(C#N)c3c2C(=O)NCC3)cc1
Agent: [Cu]I
Agent: O=C([O-])[O-]
Agent: [K+]
Product: COc1ccc(-n2nc(C#N)c3c2C(=O)N(c2ccc(C(C)(C)CN4CCCC4=O)cc2)CC3)cc1
Temperature: 130 °C

Procedure:
To 1-(4-methoxy-phenyl)-7-oxo-4,5,6,7-tetrahydro-1H-pyrazolo[3,4-c]pyridine-3-carbonitrile (0.149 g, 0.55 mmol), 1-[2-(4-iodo-phenyl)-2-methyl-propyl]-pyrrolidin-2-one (0.19 g, 0.55 mmol), and K2CO3 (0.23 g, 1.7 mmol) was added degassed DMSO (4 mL) followed by CuI (21 mg, 0.11 mmol). The mixture was heated to 130° C. for 5 h. The reaction was cooled, partitioned between ethyl acetate and water, extracted with ethyl acetate, and dried (MgSO4). Chromatography on silica gel using 0–5% MeOH in CH2Cl2 followed by further purification by HPLC afforded the title
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([N+:14]([O-:16])=[O:15])[CH:13]=1)[C:8](Cl)=[O:9])=[O:4].CC(C)=O.[NH2:21][CH2:22][C:23]([OH:25])=[O:24].C(=O)(O)[O-].[Na+]>O>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]([CH:11]=[C:12]([N+:14]([O-:16])=[O:15])[CH:13]=1)[C:8]([NH:21][CH2:22][C:23]([OH:25])=[O:24])=[O:9])=[O:4]
Reactant: COC(=O)c1cc(C(=O)Cl)cc([N+](=O)[O-])c1
Reactant: NCC(=O)O
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(C)=O
Solvent: O
Product: COC(=O)c1cc(C(=O)NCC(=O)O)cc([N+](=O)[O-])c1

Procedure:
Under agitation and during the course of 21/2 hours, 183.0 g. (0.75 mole) of 3-methoxycarbonyl-5-nitrobenzoyl chloride in 750 ml. of acetone is added dropwise to a solution of 62.0 g. (0.825 mole) of glycine and 189.0 G. of sodium bicarbonate in 3 l. of water. The first-obtained precipitate is gradually dissolved again after an additional three hours of agitation. Thereafter, the reaction mixture is extracted twice with ether, the aqueous phase is acidified with concentrated hydrochloric acid, the thus-precipitated oil is extracted repeatedly with ethyl acetate, and the combined ethyl acetate extracts, after washing with water and drying with sodium sulfate, are mixed with a stoichiometric amount of dicyclohexylamine. After allowing the reaction mixture to stand for some time, it is filtered off from the precipitated dicyclohexylammonium salt (m.p. 204°-205° C. form chloroform/ether), washed several times with ether, and the acid is liberated again by distributing the reaction mixture between ethyl acetate and 2 N sulfuric acid. After washing the ethyl phases with water, drying with sodium sulfate, and concentrating under vacuum, 181.0 g. of the above-identified compound is obtained. M.P. 142°-143° C.
Reaction SMILES: [Cl:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][C:13]([CH2:17][OH:18])=[C:12]2[N:19]1[CH:23]=[CH:22][N:21]=[CH:20]1)=[O:5].N1C=CC=CC=1.Cl[C:36]([O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:37]>ClCCl>[Cl:1][C:2]1[CH:27]=[CH:26][CH:25]=[C:24]([Cl:28])[C:3]=1[C:4]([NH:6][C:7]1[CH:8]=[CH:9][CH:10]=[C:11]2[C:16]=1[N:15]=[CH:14][C:13]([CH2:17][O:18][C:36]([O:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:37])=[C:12]2[N:19]1[CH:23]=[CH:22][N:21]=[CH:20]1)=[O:5]
Reactant: O=C(Nc1cccc2c(-n3ccnc3)c(CO)cnc12)c1c(Cl)cccc1Cl
Reactant: O=C(Cl)Oc1ccccc1
Solvent: ClCCl
Solvent: c1ccncc1
Product: O=C(OCc1cnc2c(NC(=O)c3c(Cl)cccc3Cl)cccc2c1-n1ccnc1)Oc1ccccc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 9.7 %

Procedure:
To a suspension of 8-(2,6-dichlorobenzoylamino)-3-hydroxymethyl-4-(imidazol-1-yl)quinoline (800 mg) in dichloromethane (10 ml) were dropwise added pyridine (230 mg) and phenyl chloroformate (333 mg) at ambient temperature, and the mixture was stirred for 1 hour at ambient temperature. The mixture was washed with saturated ammonium chloride solution, saturated sodium bicarbonate solution and brine, dried over magnesium sulfate and evaporated in vacuo. The residue was purified by column chromatography on silica gel (ethyl acetate-n-hexane) to give 8-(2,6-dichlorobenzoylamino)-4-(imidazol-1-yl)-3-(phenoxycarbonyloxymethyl)quinoline (100 mg).
Reaction SMILES: [CH2:1]1[C@@H:10]2[C@@H:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:2]1.[C:11](C(C)=O)([CH3:13])=[O:12].[OH:17]N1C(=O)C2=CC=CC=C2C1=O.O=O>C(O)(=O)C>[C:11]([C@@:5]12[CH2:6][CH2:7][CH2:8][CH2:9][C@:10]1([OH:17])[CH2:1][CH2:2][CH2:3][CH2:4]2)(=[O:12])[CH3:13]
Reactant: O=C1c2ccccc2C(=O)N1O
Reactant: CC(=O)C(C)=O
Reactant: C1CC[C@H]2CCCC[C@H]2C1
Agent: O=O
Solvent: CC(=O)O
Product: CC(=O)[C@]12CCCC[C@@]1(O)CCCC2

Procedure:
A mixture of 0.1 mol of cis-decalin, 0.5 mol of biacetyl, 10 mmol of N-hydroxyphthalimide, 1 mmol of acetylacetonatocobalt(II), and 100 ml of acetic acid was stirred at 75° C. in an oxygen atmosphere at atmospheric pressure for 4 hours. The reaction mixture was concentrated to about 20% by weight and was then extracted with ethyl acetate, and the extract was concentrated and was then washed with hexane to yield 4a-acetyl-8a-hydroxy-cis-decalin (yield: 30%). The conversion rate from cis-decalin was 68%.
Reaction SMILES: [C:1]1(=[O:6])[CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:7][CH:8]([CH2:11][CH2:12][CH3:13])[CH:9]=O.[O-2].[Pr+3].[O-2].[O-2].[Pr+3]>[Pd]>[CH3:7][CH:8]([CH2:11][CH2:12][CH3:13])[CH2:9][CH:2]1[CH2:3][CH2:4][CH2:5][C:1]1=[O:6]
Reactant: CCCC(C)C=O
Reactant: O=C1CCCC1
Agent: [Pd]
Agent: [O-2]
Agent: [Pr+3]
Product: CCCC(C)CC1CCCC1=O
Temperature: 150 °C
Yield: 89 %

Procedure:
A mixture of 126 g (1.5 moles) of cyclopentanone, 50 g (0.5 mole) of 2-methylpentanal and 10 g of a pulverulent catalyst containing 1% by weight of palladium, 94% by weight of alumina and 5% by weight of praseodymium oxide was initially taken in a 300 ml autoclave. The autoclave was flushed with nitrogen and hydrogen at 20° C., after which H2 was forced in to a pressure of 10 bar and the reaction mixture was then heated at 150° C. under a hydrogen pressure of 30 bar until the pressure remained constant. The catalyst was removed, after which the mixture discharged from the autoclave was fractionated. 74.9 g of pure 2-(2-methylpentyl)-cyclopentanone (bp. 125° C./20 mbar) were obtained, corresponding to a selectivity of 89.2%, based on 2-methylpentanal.
Reaction SMILES: C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[S:20]([Cl:24])(Cl)(=[O:22])=[O:21].C([N+](CCCC)(CCCC)CCCC)CCC.[Br:42][C:43]1[N:48]=[CH:47][C:46](/[CH:49]=[CH:50]/S(O)(=O)=O)=[CH:45][CH:44]=1>ClCCl>[Br:42][C:43]1[N:48]=[CH:47][C:46](/[CH:49]=[CH:50]/[S:20]([Cl:24])(=[O:22])=[O:21])=[CH:45][CH:44]=1
Reactant: O=S(=O)(O)/C=C/c1ccc(Br)nc1
Reactant: O=S(=O)(Cl)Cl
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: ClCCl
Product: O=S(=O)(Cl)/C=C/c1ccc(Br)nc1
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 37.1 %

Procedure:
Triphenylphosphine (2.74 g, 10.44 mmol) was dissolved in anhydrous dichloromethane (30 mL) under an atmosphere of argon and the mixture was cooled to 0° C. with an ice bath. Sulfuryl chloride (0.87 mL, 10.68 mmol) was added dropwise and the cooling bath was removed. The solution was stirred at ambient temperature for 15 min. A solution of (E)-2-(6-bromopyridin-3-yl)ethenesulfonic acid tetrabutylammonium (2.46 g, 4.86 mmol) in anhydrous dichloromethane (10 mL) was added dropwise over 10 min. The reaction was stirred at ambient temperature for 1.5 h and the mixture was concentrated. Purification by column chromatography, using a gradient of 5-30% ethyl acetate in heptane as the eluent, gave 0.51 g of the title compound.
Reaction SMILES: [NH2:1][C@@H:2]([CH2:7][CH2:8][S:9][CH3:10])[C:3]([O:5][CH3:6])=[O:4].[C:11]([NH:18][CH2:19][C:20](O)=[O:21])([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12].C(N=C=NC(C)C)(C)C.C(N(C(C)C)CC)(C)C>ClCCl>[CH3:15][C:14]([CH3:17])([CH3:16])[O:13][C:11](=[O:12])[NH:18][CH2:19][C:20](=[O:21])[NH:1][C@H:2]([C:3]([O:5][CH3:6])=[O:4])[CH2:7][CH2:8][S:9][CH3:10]
Reactant: COC(=O)[C@@H](N)CCSC
Reactant: CC(C)(C)OC(=O)NCC(=O)O
Agent: CC(C)N=C=NC(C)C
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)[C@H](CCSC)NC(=O)CNC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.2 %

Procedure:
To a solution of (S)-methyl 2-amino-4-(methylthio)butanoate (5 g, 30.7 mmol) and Boc-glycine (6.4 g, 36.8 mmol) in dichloromethane (100 mL) at room temperature was added diisopropylcarbodiimide (4.6 g, 36.8 mmol) and diisopropylethylamine (4.75 g, 36.8 mmol). The mixture was stirred overnight at room temperature, washed with 1N HCl, brine, and dried over sodium sulfate, filtered and concentrated to give a residue, which was purified on silica gel column to give (S)-methyl 12,12-dimethyl-7,10-dioxo-11-oxa-2-thia-6,9-diazatridecane-5-carboxylate (7 g, 71%). MS calcd for (C13H24N2O5S+H)+: 321.1; MS found: (M+H)+=321.2.
Reaction SMILES: [Cl:1][C:2]1[C:3]([SH:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[C:12](OC(=O)C)(=[O:14])[CH3:13].Cl>C(O)(=O)C>[C:12]([S:11][C:3]1[C:2]([Cl:1])=[CH:10][CH:9]=[CH:8][C:4]=1[C:5]([OH:7])=[O:6])(=[O:14])[CH3:13]
Reactant: O=C(O)c1cccc(Cl)c1S
Reactant: CC(=O)OC(C)=O
Agent: Cl
Solvent: CC(=O)O
Product: CC(=O)Sc1c(Cl)cccc1C(=O)O

Procedure:
3-Chloro-2-mercaptobenzoic acid (9.8 g, 52 mmol), acetic anhydride (6.3 g, 62 mmol) and glacial acetic acid (22 ml) were heated at 80° C. for 4 hours, then cooled and mixed with dilute hydrochloric acid. The crystalline product was filtered.
Reaction SMILES: [NH2:1][C:2]([NH2:4])=[S:3].[Cl:5][C:6]1[C:7](=[O:15])[NH:8][C:9](=[O:14])[NH:10][C:11]=1[CH2:12]Cl>C(O)C>[ClH:5].[Cl:5][C:6]1[C:7](=[O:15])[NH:8][C:9](=[O:14])[NH:10][C:11]=1[CH2:12][S:3][C:2](=[NH:4])[NH2:1]
Reactant: NC(N)=S
Reactant: O=c1[nH]c(CCl)c(Cl)c(=O)[nH]1
Solvent: CCO
Product: Cl
Product: N=C(N)SCc1[nH]c(=O)[nH]c(=O)c1Cl
Yield: 161.6 %

Procedure:
To a solution of 140 mg of thiourea in ethanol (3 ml), 300 mg of 5-chloro-6-chloromethyluracil were added, followed by heating for 6 hours under reflux. After the reaction mixture was allowed to cool down, a crystallized matter was collected by filtration, whereby 337 mg of the title compound were obtained (yield: 81%).
Reaction SMILES: [C:1]1([CH3:9])[C:2]([CH:7]=O)=[CH:3][CH:4]=[CH:5][CH:6]=1.[C:10]([NH2:14])([CH3:13])([CH3:12])[CH3:11]>C1(C)C=CC=CC=1>[CH3:9][C:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH:7]=[N:14][C:10]([CH3:13])([CH3:12])[CH3:11]
Reactant: CC(C)(C)N
Reactant: Cc1ccccc1C=O
Solvent: Cc1ccccc1
Product: Cc1ccccc1C=NC(C)(C)C
Yield: 92.1 %

Procedure:
A stirred solution of o-tolualdehyde (25 g, 0.21 mol), and t-butylamine (27.75 g, 0.38 mol) in toluene (250 mL) was refluxed under standard Dean-Stark conditions for 20 h. The solution was evaporated to an oil which was vacuum distilled (bp 70°-73° C., 0.6 mm Hg) to afford 33.9 g (93%) of product: IR (neat) 2980, 1645, 1605, 1460, 1375, 1210, 960, 910 cm-1 ; 1H NMR (400 MHz, CDCl3) δ 8.56 (s, 1 H), 7.86-7.83 (m, 1 H), 7.25-7.11 (m, 3 H), 2.46 (s, 3 H), 1.30 (s, 9 H); 13C NMR (CDCl3, 100 MHz) δ 153.7, 137.1, 135.1, 130.5, 129.6, 127.1, 126.4, 57.5, 29.8, 19.2; GC RT 7.6 min (DB-1, 30 m×0.53 mm, program: 100° C. for 5 min, 100°-260° C. at 15° C./min, hold at 260° C. for 12 min).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:10]([CH3:11])=[CH:9][C:8]([Cl:12])=[CH:7][C:6]=1[CH3:13])=O.[NH2:14][C:15]([NH2:17])=[S:16]>CCO>[Cl:12][C:8]1[CH:9]=[C:10]([CH3:11])[C:5]([C:3]2[N:14]=[C:15]([NH2:17])[S:16][CH:2]=2)=[C:6]([CH3:13])[CH:7]=1
Reactant: NC(N)=S
Reactant: Cc1cc(Cl)cc(C)c1C(=O)CBr
Solvent: CCO
Product: Cc1cc(Cl)cc(C)c1-c1csc(N)n1
Yield: 72 %

Procedure:
A mixture of 2-bromo-1-(4-chloro-2,6-dimethylphenyl)ethanone (6.54 g, 25.0 mmol) and thiourea (1.90 g, 25.0 mmol) in 95% EtOH (35.7 mL) was heated at reflux for 60 min. The solution was concentrated and added with water (50 mL) followed by saturated aqueous Na2CO3 (4.0 mL). The resultant precipitate was filtered and recrystallized in toluene (30 mL). The solids were filtered and dried under vacuum to give 4-(4-chloro-2,6-dimethylphenyl)thiazol-2-amine (4.30 g) as white solids in 72% yield: 1H NMR (500 MHz, DMSO-d6) δ 7.16 (s, 2 H), 6.43 (s, 1 H), 2.10 (s, 6 H).