Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C@H:2]1[CH2:7][CH2:6][N:5]([C:8]2[CH:13]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:11]=[C:10]([CH3:18])[N:9]=2)[CH2:4][C@H:3]1[O:19][CH3:20].[Cl:21][C:22]1[N:23]=[C:24]([C:29](O)=[O:30])[NH:25][C:26]=1[CH2:27][CH3:28].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1>>[Cl:21][C:22]1[N:23]=[C:24]([C:29]([NH:1][C@H:2]2[CH2:7][CH2:6][N:5]([C:8]3[CH:13]=[C:12]([C:14]([O:16][CH3:17])=[O:15])[CH:11]=[C:10]([CH3:18])[N:9]=3)[CH2:4][C@H:3]2[O:19][CH3:20])=[O:30])[NH:25][C:26]=1[CH2:27][CH3:28]
Reactant: COC(=O)c1cc(C)nc(N2CC[C@H](N)[C@H](OC)C2)c1
Reactant: CCc1[nH]c(C(=O)O)nc1Cl
Agent: CCN=C=NCCCN(C)C
Agent: Cl
Agent: On1nnc2ccccc21
Product: CCc1[nH]c(C(=O)N[C@H]2CCN(c3cc(C(=O)OC)cc(C)n3)C[C@H]2OC)nc1Cl

Procedure:
The same operation as in Example (1g) was performed using methyl cis(±)-2-(4-amino-3-methoxypiperidin-1-yl)-6-methylpyridine-4-carboxylate obtained in Example (166b) (23.9 mg, 0.44 mmol), 4-chloro-5-ethyl-1H-imidazole-2-carboxylic acid obtained by the method described in Example (1d) (14 mg, 0.08 mmol), WSC hydrochloride (46.8 mg, 0.24 mmol) and HOBt (11 mg, 0.08 mmol), to obtain 30.4 mg of the title compound as a pale yellow oily substance (86%).
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([N:10]2[C:22](=[O:23])[C:13]3=[CH:14][NH:15][C:16]4[C:21]([N:12]3[C:11]2=[O:24])=[CH:20][CH:19]=[CH:18][CH:17]=4)=[CH:6][CH:5]=1)[CH3:2].[CH3:25]OC(OC)N(C)C>CN(C=O)C>[CH3:25][N:15]1[C:16]2[C:21](=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:12]2[C:11](=[O:24])[N:10]([C:7]3[CH:6]=[CH:5][C:4]([O:3][CH2:1][CH3:2])=[CH:9][CH:8]=3)[C:22](=[O:23])[C:13]2=[CH:14]1
Reactant: CCOc1ccc(-n2c(=O)c3c[nH]c4ccccc4n-3c2=O)cc1
Reactant: COC(OC)N(C)C
Solvent: CN(C)C=O
Product: CCOc1ccc(-n2c(=O)c3cn(C)c4ccccc4n-3c2=O)cc1
Temperature: 100 °C

Procedure:
2-(4-Ethoxyphenyl)-imidazo[1,5,a]quinoxaline-1,3(2H,5H)-dione (100 mg) was added to a solution of dimethylformamide dimethylacetal (10 ml,) and DMF (5 mL), and the reaction mixture was heated to 100° C. for 4 h. The solution was cooled to room temperature and poured onto water (200 mL). The resulting precipitate was collected and dried to yield 5-N-Methyl-2-(4-ethoxyphenyl)-imidazo[1,5,a]quinoxaline-1,3(2H,5H)-dione (Compound 42). m.p. 263-266° C.
Reaction SMILES: [CH:1]([OH:3])=[O:2].C(OC(=O)C)(=O)C.O[CH2:12][CH2:13][N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=[C:16]([C:24]([OH:26])=[O:25])[C:15]1=[O:27]>N1C=CC=CC=1>[CH:1]([O:3][CH2:12][CH2:13][N:14]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=[C:16]([C:24]([OH:26])=[O:25])[C:15]1=[O:27])=[O:2]
Reactant: O=C(O)c1nc2ccccc2n(CCO)c1=O
Reactant: O=CO
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: O=COCCn1c(=O)c(C(=O)O)nc2ccccc21
Temperature: 25 °C
Reaction time: 6 h

Procedure:
Formic acid (3 ml., 98%) was added dropwise to acetic anhydride (6 ml) which was cooled below 5°. The mixture was heated at 50° for 15 minutes and cooled to below 5° and added slowly to a cold (5°-10°) solution of 3,4-dihydro-4(2-hydroxyethyl)-3-oxo-2-quinoxalinecarboxylic acid (3.2 g) in pyridine (40 ml). The solution was allowed to warm to room temperature, stirred for 6 hours and the pyridine was distilled off under reduced pressure. Hydrochloric acid (50 ml., 2N) was added to the residue and the solid was filtered off and dried, m.p. > 100°. Attempts to recrystallise this compound from dimethylformamide resulted in the loss of the formyl group.
Reaction SMILES: C(O[C:6](=O)[N:7]([CH2:9][CH2:10][C:11]1[C:19]2[NH:18][C:17](=[O:20])[N:16]([CH2:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:15]=2[CH:14]=[CH:13][CH:12]=1)C)(C)(C)C.[ClH:29].CCO.C(OCC)C>O1CCCC1>[ClH:29].[CH2:21]([N:16]1[C:15]2[CH:14]=[CH:13][CH:12]=[C:11]([CH2:10][CH2:9][NH:7][CH3:6])[C:19]=2[NH:18][C:17]1=[O:20])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1
Reactant: CN(CCc1cccc2c1[nH]c(=O)n2Cc1ccccc1)C(=O)OC(C)(C)C
Agent: Cl
Solvent: C1CCOC1
Solvent: CCOCC
Solvent: CCO
Product: CNCCc1cccc2c1[nH]c(=O)n2Cc1ccccc1

Procedure:
[2-(1-Benzyl-2-oxo-2,3-dihydro-1H-benzoimidazol-4-yl)-ethyl]-methyl-carbamic acid tert-butyl ester (31 mg) was dissolved in 2.0 ml of tetrahydrofuran and 100 uL of 2.0 N HCl/EtOH was added. The solution was heated on a steam bath for 30 minutes and then after cooling diethyl ether was slowly added to produce 10 mg of 1-benzyl-4-(2-methylamino-ethyl)-1,3-dihydro-benzoimidazol-2-one hydrochloride salt as a colorless powder. MS: 282 (M+H)−.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH:2]1[O:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][C:15]([NH2:17])=O.[H-].[Al+3].[Li+].[H-].[H-].[H-].[O:24]1CCC[CH2:25]1>>[NH2:17][CH2:15][CH2:14][CH2:13][CH2:12][CH:11]([CH2:10][CH2:9][CH2:8][O:7][CH:2]1[CH2:3][CH2:4][CH2:5][CH2:6][O:1]1)[CH2:25][OH:24]
Reactant: NC(=O)CCCCCCCOC1CCCCO1
Reactant: C1CCOC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Product: NCCCCC(CO)CCCOC1CCCCO1
Reaction time: 0.25 h

Procedure:
A solution of 1.0 g (3.17 mmol) of 5-[3-(tetrahydropyranyloxy)propyl]valeramide in 5 ml tetrahydrofuran is added dropwise to a suspension of 0.481 g (12.68 mmol) lithium aluminium hydride in 20 ml dry tetrahydrofuran. The reaction mixture is refluxed for 2.5 h, cooled in an ice-bath and quenched by the addition of 0.5 ml water, 0.5 ml 15% aqueous sodium hydroxide followed by 1.5 ml water. The mixture is stirred for 15 min and filtered, washed and then subjected to evaporation to give 6-amino-2-[3-(tetrahydropyranyloxy)propyl]-hexan-1-ol.
Reaction SMILES: [SH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[C:9]([CH3:17])([N:11]2[CH2:16][CH2:15][O:14][CH2:13][CH2:12]2)[CH3:10])=[CH:4][CH:3]=1.[CH2:19](Br)[CH:20]=[CH2:21].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[CH2:21]([S:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:18])[C:9]([CH3:10])([N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[CH3:17])=[CH:4][CH:3]=1)[CH:20]=[CH2:19]
Reactant: C=CCBr
Reactant: CC(C)(C(=O)c1ccc(S)cc1)N1CCOCC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: C=CCSc1ccc(C(=O)C(C)(C)N2CCOCC2)cc1

Procedure:
10 g (0.38 mol) of 1-(4-mercaptophenyl)-2-methyl-2-morpholinopropan-1-one, 5 g (0.041 mol) of freshly distilled allylbromide and 5.2 g (0.038 mol) of dry potassium carbonate are suspended in 50 ml of acetone and the mixture is heated to reflux temperature for 16 hours. After cooling, the solvent is removed by distillation, water and diethyl ether are added to the residue, and the water phase is extracted with ether. The organic phase is washed with 10% NaOH solution and water, dried over MgSO4 and concentrated. The oil which remains is distilled in a bulb tube at 180°-200° C./13 Pa. (Compound No. 23).
Reaction SMILES: [CH2:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:3][C:2]1=O.[C:11]([O:15][C:16](=[O:30])[C@H:17]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[NH:18][C:19](=[O:22])[CH2:20][NH2:21])([CH3:14])([CH3:13])[CH3:12].C([BH3-])#N.[Na+].Cl.P(=O)(O)(O)O.[C:41]([OH:46])(=[O:45])[C:42]([OH:44])=[O:43]>CO.CCOCC.C(O)C>[C:41]([OH:46])(=[O:45])[C:42]([OH:44])=[O:43].[C:11]([O:15][C:16](=[O:30])[C@H:17]([CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)[NH:18][C:19](=[O:22])[CH2:20][NH:21][CH:2]1[CH2:3][C:4]2[C:9](=[CH:8][CH:7]=[CH:6][CH:5]=2)[CH2:1]1)([CH3:14])([CH3:12])[CH3:13]
Reactant: O=C1Cc2ccccc2C1
Reactant: CC(C)(C)OC(=O)[C@H](Cc1ccccc1)NC(=O)CN
Agent: Cl
Agent: O=C(O)C(=O)O
Agent: O=P(O)(O)O
Solvent: CO
Solvent: CCO
Solvent: CCOCC
Product: CC(C)(C)OC(=O)[C@H](Cc1ccccc1)NC(=O)CNC1Cc2ccccc2C1
Reaction time: 8 h
Yield: 50.2 %

Procedure:
2-Indanone (3.6 g) and glycyl-L-phenylalanine tert-butyl ester (7.3 g) are dissolved in 50 ml of methanol and 3 g of sodium cyanoborohydride is added in small portions at room temperature. Then, 0.5 ml of ethanolic solution of 7N hydrogen chloride (0.5 ml) is added dropwise and the mixture is allowed to stand at room temperature overnight. To the reaction mixture are added 50 ml of methanol and 200 ml of 10% phosphoric acid, followed by extraction with a mixture of ether (100 ml) and petroleum ether (100 ml). The aqueous layer is made neutral with sodium hydrogen carbonate and extracted twice with 200 ml portions of ethyl acetate. The extracts are combined, dried over anhydrous magnesium sulfate, and distilled to remove the solvent, whereby a yellow-colored oil is obtained. This product is dissolved in ether and a solution of 2 g of oxalic acid in a small quantity of ethanol is added. The resulting crystalline precipitate is collected by filtration and dried to give 5.4 g of N-(2-indanyl)glycyl-L-phenylalanine tert-butyl ester oxalate. The product is added to a mixture of 20 ml of methanol and 100 ml of water and made alkaline by dropwise addition of 1N sodium hydroxide with stirring. The crystalline precipitate is collected by filtration and dried to give 4 g of free N-(2-indanyl)glycyl-L-phenylalanine tert-butyl ester melting at 117°-120° C.
Reaction SMILES: [C:1]([O:5][C:6](=[O:33])[N:7]([C:15]1[C:20]([C:21]2[O:22][C:23]([C:26]3[S:27][CH:28]=[CH:29][C:30]=3[CH3:31])=[N:24][N:25]=2)=[N:19][C:18](Br)=[CH:17][N:16]=1)C(OC(C)(C)C)=O)([CH3:4])([CH3:3])[CH3:2].CC1(C)C(C)(C)OB([C:42]2[CH:47]=[CH:46][C:45]([S:48]([CH:51]3[CH2:56][CH2:55][CH2:54][N:53]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:52]3)(=[O:50])=[O:49])=[CH:44][CH:43]=2)O1.O.C([O-])([O-])=O.[Na+].[Na+]>CC#N>[C:1]([O:5][C:6]([NH:7][C:15]1[N:16]=[CH:17][C:18]([C:42]2[CH:47]=[CH:46][C:45]([S:48]([CH:51]3[CH2:56][CH2:55][CH2:54][N:53]([C:57]([O:59][C:60]([CH3:63])([CH3:62])[CH3:61])=[O:58])[CH2:52]3)(=[O:50])=[O:49])=[CH:44][CH:43]=2)=[N:19][C:20]=1[C:21]1[O:22][C:23]([C:26]2[S:27][CH:28]=[CH:29][C:30]=2[CH3:31])=[N:24][N:25]=1)=[O:33])([CH3:4])([CH3:2])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCCC(S(=O)(=O)c2ccc(B3OC(C)(C)C(C)(C)O3)cc2)C1
Reactant: Cc1ccsc1-c1nnc(-c2nc(Br)cnc2N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)o1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: CC#N
Product: Cc1ccsc1-c1nnc(-c2nc(-c3ccc(S(=O)(=O)C4CCCN(C(=O)OC(C)(C)C)C4)cc3)cnc2NC(=O)OC(C)(C)C)o1
Temperature: 65 °C
Yield: 106.2 %

Procedure:
tert-butyl-N-[5-bromo-3-[5-(3-methyl-2-thienyl)-1,3,4-oxadiazol-2-yl]pyrazin-2-yl]-N-tert-butoxycarbonyl-carbamate (750 mg, 1.393 mmol) and tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (691.5 mg, 1.532 mmol) were suspended in MeCN (7.500 mL)/water (7.500 mL) and Na2CO3 (1.393 mL of 2 M, 2.786 mmol) was added. The reaction mixture was degassed with 3× nitrogen/vacuum cycles. Pd(tBu3P)2 (71.19 mg, 0.1393 mmol) was added and the reaction mixture again degassed 3 times then heated to 65° C. (Dry Syn Temp) for 1.5 hours. The reaction mixture was cooled to ambient temperature and diluted with ethylacetate/water. The aqueous layer was extracted with ethylacetate (×1) and the combined organic extracts washed with brine (×2), dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by column chromatography (ISCO Companion, 80 g column, eluting with 0 to 30% ethyl acetate/petroleum Ether, (loaded in DCM) to give the sub-title product as a yellow solid (1.01 g, 93% Yield). H NMR (400.0 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.59 (d, 2H), 8.16 (d, 2H), 7.96 (d, 1H), 7.24 (d, 1H), 4.14-3.92 (m, 1H), 3.77 (br d, 1H), 3.44 (br s, 1H), 3.02-2.91 (m, 1H), 2.79 (br t, 1H), 2.67 (s, 3H), 2.05 (br s, 1H), 1.76-1.58 (m, 2H) and 1.35-1.22 (m, 28H) ppm; LC/MS m/z 627 [M−100−56]+.
Reaction SMILES: Br[C:2]1[CH:22]=[C:5]2[S:6][CH:7]=[C:8]([C:9]3[C:14]([O:15][CH3:16])=[CH:13][C:12]([CH2:17][O:18][CH3:19])=[CH:11][C:10]=3[O:20][CH3:21])[N:4]2[N:3]=1.[CH3:23][S:24]([O-:26])=[O:25].[Na+].N1CCC[C@H]1C(O)=O.[OH-].[Na+]>[Cu](I)I.O.CS(C)=O>[CH3:21][O:20][C:10]1[CH:11]=[C:12]([CH2:17][O:18][CH3:19])[CH:13]=[C:14]([O:15][CH3:16])[C:9]=1[C:8]1[N:4]2[N:3]=[C:2]([S:24]([CH3:23])(=[O:26])=[O:25])[CH:22]=[C:5]2[S:6][CH:7]=1
Reactant: COCc1cc(OC)c(-c2csc3cc(Br)nn23)c(OC)c1
Reactant: CS(=O)[O-]
Agent: I[Cu]I
Agent: O=C(O)[C@@H]1CCCN1
Agent: [Na+]
Solvent: O
Solvent: CS(C)=O
Product: COCc1cc(OC)c(-c2csc3cc(S(C)(=O)=O)nn23)c(OC)c1
Temperature: 140 °C
Yield: 89.7 %

Procedure:
To a dimethyl sulfoxide (28.0 mL) solution of 6-bromo-3-[2,6-dimethoxy-4-(methoxymethyl)phenyl]pyrazolo[5,1-b][1,3]thiazole (1.12 g, 2.92 mmol) were added sodium methanesulphinate (2.38 g, 23.3 mmol), L-proline (268 mg, 2.33 mmol), sodium hydroxide (184 mg, 4.61 mmol), and copper iodide (444 mg, 2.33 mmol) and the mixture was heated at 140° C. for three hours by using Biotage Initiator™ Microwave Synthesizer. After the reaction was completed, water was added, the reaction mixture was extracted with ethyl acetate, the organic layer was dried over magnesium sulfate, and the solvent was distilled off under reduced pressure. To the residue, ethyl acetate was added, and the obtained solid was subjected to suction filtration and dried to obtain the title compound (1.00 g, 2.62 mmol).
Reaction SMILES: Br[O-:2].[Na+].[C:4]([C:7]1[CH:16]=[C:15]([O:17][CH3:18])[C:14]2[C:13]([CH3:20])([CH3:19])[CH2:12][CH2:11][C:10]([CH3:22])([CH3:21])[C:9]=2[C:8]=1[O:23][CH3:24])(=[O:6])C>O1CCOCC1.O>[CH3:24][O:23][C:8]1[C:9]2[C:10]([CH3:22])([CH3:21])[CH2:11][CH2:12][C:13]([CH3:20])([CH3:19])[C:14]=2[C:15]([O:17][CH3:18])=[CH:16][C:7]=1[C:4]([OH:6])=[O:2]
Reactant: [O-]Br
Reactant: COc1cc(C(C)=O)c(OC)c2c1C(C)(C)CCC2(C)C
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: COc1cc(C(=O)O)c(OC)c2c1C(C)(C)CCC2(C)C
Reaction time: 8 h

Procedure:
In a second stage, this hypobromite solution is slowly added to a stirred solution, cooled to about 5° C., of 43 g of 2-acetyl-1,4-dimethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro naphthalene, obtained in stage (b) above, in 500 cm3 of dioxane. The rate of introduction is such that the temperature does not exceed 15° C. The reaction mixture is then left to stand overnight, diluted with 300 cm3 of water, then, at a temperature lower than 20° C., the excess sodium hypobromite is destroyed by the slow addition of a 25% aqueous solution of sodium bisulfite. The expected acid is then precipitated by acidifying the mixture by the addition of 380 cm3 of 6N HCl. The precipitate is filtered, washed with water and dried under reduced pressure. 40.8 g of 1,4-dimethoxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydro-2-naphthalene carboxylic acid are obtained in the form of a white solid having a melting point of 187° C.
Reaction SMILES: [SH:1][C:2]1[NH:3][C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=1.Br[CH:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:13]([OH:15])=[O:14]>CC(C)=O>[NH:3]1[C:4]2[CH:10]=[CH:9][CH:8]=[CH:7][C:5]=2[N:6]=[C:2]1[S:1][CH:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[C:13]([OH:15])=[O:14]
Reactant: Sc1nc2ccccc2[nH]1
Reactant: O=C(O)C(Br)c1ccccc1
Solvent: CC(C)=O
Product: O=C(O)C(Sc1nc2ccccc2[nH]1)c1ccccc1
Yield: 92 %

Procedure:
An acetone solution of 13.5 g (0.09M) of 2-mercaptobenzimidazole and 19.4 g (0.09M) of α-bromophenylacetic acid containing 10 ml glacial acetic acid is heated for 3 hours. The solid HBr salt upon removal of the solvent is disproportionated by stirring in 1 L of water. The crude material is recrystallied from aqueous acetone. The recrystallized material weighs 24.0 g (92% yield) and melts at 187°-8° C. dec.
Reaction SMILES: [NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([N+]([O-])=O)=[CH:4][C:3]=1[C:21]([O:23][C:24]1C=CC=CC=1)=[O:22].C(=O)([O-])[O-].[K+].[K+].[Cl:36][C:37]1[CH:42]=[CH:41][C:40]([SH:43])=[CH:39][CH:38]=1.CN1CCCC1=O>CO>[NH2:1][C:2]1[C:15]2[C:14](=[O:16])[C:13]3[C:8](=[CH:9][CH:10]=[CH:11][CH:12]=3)[C:7](=[O:17])[C:6]=2[C:5]([S:43][C:40]2[CH:41]=[CH:42][C:37]([Cl:36])=[CH:38][CH:39]=2)=[CH:4][C:3]=1[C:21]([O:23][CH3:24])=[O:22]
Reactant: Nc1c(C(=O)Oc2ccccc2)cc([N+](=O)[O-])c2c1C(=O)c1ccccc1C2=O
Reactant: Sc1ccc(Cl)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Solvent: CN1CCCC1=O
Product: COC(=O)c1cc(Sc2ccc(Cl)cc2)c2c(c1N)C(=O)c1ccccc1C2=O
Temperature: 80 °C

Procedure:
11.6 g of phenyl 1-amino-4-nitroanthraquinone-2-carboxylate (see Example 3a), 4.2 g of potassium carbonate (anhydrous) and 4.8 g of 4-chlorothiophenol are introduced into 50 cc of N-methylpyrrolidone, and the mixture is heated at 80° C. until the starting material has reacted completely. The mixture is then diluted at 70° C. with 50 cc of methanol and is allowed to cool. The crystals which have separated out are filtered off with suction, washed with methanol and hot water and dried. This gives 8.3 g, corresponding to 65% of theory, of methyl 1-amino-4-(4-chlorophenylmercapto)-anthraquinone-2-carboxylate, which has been formed by reacting the phenyl ester with the methanol used for the precipitation. The dyestuff can be purified by recrystallisation from dimethylformamide.
Reaction SMILES: [CH2:1]([O:3][C:4]([CH:6]([CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:18])[CH2:13][CH2:12]1)[CH2:7][C:8](C)=[CH2:9])=[O:5])[CH3:2].I([O-])(=O)(=O)=[O:28].[Na+]>O1CCCC1.O.S([O-])([O-])=O.[Na+].[Na+].C(=O)(O)[O-].[Na+].[Os](=O)(=O)(=O)=O>[CH2:1]([O:3][C:4]([CH:6]([CH:11]1[CH2:16][CH2:15][N:14]([C:17]([O:19][CH2:20][C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)=[O:18])[CH2:13][CH2:12]1)[CH2:7][C:8](=[O:28])[CH3:9])=[O:5])[CH3:2]
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=C(C)CC(C(=O)OCC)C1CCN(C(=O)OCc2ccccc2)CC1
Agent: O=[Os](=O)(=O)=O
Agent: O=C([O-])O
Agent: O=S([O-])[O-]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)C(CC(C)=O)C1CCN(C(=O)OCc2ccccc2)CC1
Reaction time: 120 h

Procedure:
Osmium tetroxide (2.5 wt. % in t-BuOH; 0.3 mL, 0.001 mmol) was added to a solution of benzyl 4-[1-(ethoxycarbonyl)-3-methylbut-3-en-1-yl]piperidine-1-carboxylate (2.88 g, 8.01 mmol) in tetrahydrofuran (30 mL). Sodium periodate (5.14 g, 24.0 mmol) in water (26 mL) was added to the reaction mixture. After 5 days, the reaction was diluted with saturated aqueous sodium sulfite and saturated aqueous sodium bicarbonate and extracted with ethyl acetate (3×). The combined organic washes were dried over sodium sulfate, filtered and concentrated to give the title compound. MS 362.2 (M+1).
Reaction SMILES: C(O[C:4](=[O:10])[C:5]([O:7][CH2:8][CH3:9])=[O:6])C.[O-]CC.[Na+].CCO.[S:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21](=[O:28])[CH2:20][CH2:19]1>C1(C)C=CC=CC=1>[O:10]=[C:4]([CH:20]1[C:21](=[O:28])[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:18][CH2:19]1)[C:5]([O:7][CH2:8][CH3:9])=[O:6]
Reactant: CCOC(=O)C(=O)OCC
Reactant: O=C1CCSc2ccccc21
Agent: CC[O-]
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CCOC(=O)C(=O)C1CSc2ccccc2C1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 97.9 %

Procedure:
A solution of diethyloxalate (30.9 mL; 228.34 mmol; 1.5 eq.) in toluene (250 mL) is added dropwise at 0° C. to a solution of sodium ethoxide 21% w/w in EtOH (9.87 g; 182.67 mmol; 2 eq.). A solution of thiochroman-4-one (25 g; 152.23 mmol; 1 eq.) in toluene (250 mL) is added dropwise at 0° C. and the reaction mixture is allowed to warm up to rt. After overnight stirring, the solvent is removed and DCM (200 mL) and water (200 ml) are added. The aqueous phase is washed with DCM then acidified to pH=1-2 with 5N HCl (˜50 mL). The product is extracted with EtOAc (2×200 mL). The organic phases are combined, dried over MgSO4 and the solvent evaporated to afford 39.4 g (98%) of the title compound as an orange oil. MS (ESI+): 265.9.
Reaction SMILES: [CH:1](=[N:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N+:16]([CH2:18][C:19]([O:21][CH2:22][CH3:23])=[O:20])#[C-:17]>C(O)C>[CH2:1]([N:8]1[CH:9]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:18]([C:19]([O:21][CH2:22][CH3:23])=[O:20])[N:16]=[CH:17]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: [C-]#[N+]CC(=O)OCC
Reactant: C(=NCc1ccccc1)c1ccccc1
Solvent: CCO
Product: CCOC(=O)C1N=CN(Cc2ccccc2)C1c1ccccc1
Yield: 99.9 %

Procedure:
25.7 g (0.1305 mol) of benzylidenebenzylamine were dissolved in ethanol, and 15.2 g (0.1305 mol) of ethyl isocyanoacetate were added dropwise. The solution was heated under reflux for 16 h. Removal of the solvents and drying gave 40.2 g of the title compound as a colorless oil.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][N:15]3[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]3)=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1.FC(F)(F)C(O)=O>ClCCl>[F:1][C:2]1[CH:3]=[C:4]([C:8]2[CH:9]=[CH:10][C:11]([CH2:14][N:15]3[CH2:20][CH2:19][NH:18][CH2:17][CH2:16]3)=[N:12][CH:13]=2)[CH:5]=[CH:6][CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CCN(Cc2ccc(-c3cccc(F)c3)cn2)CC1
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Fc1cccc(-c2ccc(CN3CCNCC3)nc2)c1
Temperature: 25 °C
Reaction time: 8 h
Yield: 72 %

Procedure:
A 100 mL round-bottom flask, was charged with tert-butyl 4-[[5-(3-fluorophenyl)pyridin-2-yl]methyl]piperazine-1-carboxylate (950 mg, 2.56 mmol, 1.00 equiv), dichloromethane (15 mL), trifluoroacetic acid (2 mL). The resulting solution was stirred for overnight at room temperature. The resulting mixture was concentrated under reduced pressure to provide 500 mg (crude) of 1-[[5-(3-fluorophenyl)pyridin-2-yl]methyl]piperazine as yellow oil. LCMS (ESI, m/z): 272 [M+H]+.
Reaction SMILES: [Si]([O:8][CH2:9][C:10]1[CH:11]=[C:12]([NH:16][C:17]2[N:25]=[C:24]3[C:20]([NH:21][C:22](=[O:34])[N:23]3[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[C:19]([C:35]([O:37]CC)=O)[N:18]=2)[CH:13]=[CH:14][CH:15]=1)(C(C)(C)C)(C)C.[NH2:40]C1C(C(OCC)=O)=NC(NC2C=CC=C(CO[Si](C(C)(C)C)(C)C)C=2)=NC=1NC1C=CC=CC=1OC>ClCCl>[OH:8][CH2:9][C:10]1[CH:11]=[C:12]([NH:16][C:17]2[N:25]=[C:24]3[C:20]([NH:21][C:22](=[O:34])[N:23]3[C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[O:32][CH3:33])=[C:19]([C:35]([NH2:40])=[O:37])[N:18]=2)[CH:13]=[CH:14][CH:15]=1
Reactant: CCOC(=O)c1nc(Nc2cccc(CO[Si](C)(C)C(C)(C)C)c2)nc(Nc2ccccc2OC)c1N
Reactant: CCOC(=O)c1nc(Nc2cccc(CO[Si](C)(C)C(C)(C)C)c2)nc2c1[nH]c(=O)n2-c1ccccc1OC
Solvent: ClCCl
Product: COc1ccccc1-n1c(=O)[nH]c2c(C(N)=O)nc(Nc3cccc(CO)c3)nc21
Yield: 71 %

Procedure:
Ethyl 2-(3-((tert-butyldimethylsilyloxy)methyl)phenylamino)-9-(2-methoxyphenyl)-8-oxo-8,9-dihydro-7H-purine-6-carboxylate. Ethyl 5-amino-2-(3-((tert-butyldimethylsilyloxy)methyl)phenylamino)-6-(2-methoxyphenylamino)pyrimidine-4-carboxylate (0.242 g, 0.462 mmol) and 1,1′-1,1′-carbonyldiimidazole (0.525 g, 3.23 mmol) in dichloromethane (15 mL) were reacted according to General Procedure F and purified using biotage chromatography (10 to 90% EtOAc in hexanes) to afford the title compound (0.180 g, 71%). MS (ESI) m/z 550.5 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[CH:5]=[CH:4][C:3]=1[OH:14].[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH2:20]O)=[CH:18][CH:17]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][CH:9]([CH2:12][CH3:13])[CH2:10][CH3:11])[CH:5]=[CH:4][C:3]=1[O:14][CH2:20][C:19]1[CH:22]=[CH:23][C:16]([Cl:15])=[CH:17][CH:18]=1
Reactant: CCC(CC)Cc1ccc(O)c(Cl)c1
Reactant: OCc1ccc(Cl)cc1
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: CCC(CC)Cc1ccc(OCc2ccc(Cl)cc2)c(Cl)c1
Reaction time: 48 h
Yield: 63.4 %

Procedure:
A mixture of 0.75 g of 2-chloro-4-(2-ethylbutyl)phenol, 0.50 g of p-chlorobenzyl alcohol, 0.92 g of triphenylphosphine, 0.71 g of diisopropylazadicarboxylate and 100 mg of tetrahydrofuran was stirred at room temperatur for 48 hours. The reaction mixture was concentrated, and 50 ml of diethyl ether was added thereto. The precipitates were removed by filtration, and the filtrate was concentrated. The residue was subjected to silica gel chromatography to give 0.75 g of 2-chloro-1-(4-chlorobenzyloxy)-4-(2-ethylbutyl)benzene. Yield, 63%. nD22.6 1.5611.