Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([C:3]1[CH:8]=[CH:7][C:6]([CH:9]([CH3:18])[CH2:10][NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:14])=[O:13])=[CH:5][CH:4]=1)#[N:2].[N:19]([Sn](CCCC)(CCCC)CCCC)=[N+:20]=[N-:21].Cl>>[NH:19]1[C:1]([C:3]2[CH:8]=[CH:7][C:6]([CH:9]([CH3:18])[CH2:10][NH:11][S:12]([CH:15]([CH3:17])[CH3:16])(=[O:13])=[O:14])=[CH:5][CH:4]=2)=[N:2][N:21]=[N:20]1
Reactant: CC(CNS(=O)(=O)C(C)C)c1ccc(C#N)cc1
Reactant: CCCC[Sn](CCCC)(CCCC)N=[N+]=[N-]
Agent: Cl
Product: CC(CNS(=O)(=O)C(C)C)c1ccc(-c2nnn[nH]2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 80.8 %

Procedure:
0.2 g (0.8 mmol) of material from Example 53 and 0.5 g (1.5 mmol) of azidotributylstannane were heated to 80° C. for 72 hours. The mixture was cooled to ambient temperature, 5 mL of a saturated methanolic HCl solution was added, the mixture stirred for 30 minutes and was concentrated in vacuo. The residue was dissolved in 10 mL of acetonitrile and extracted four times with 5 mL each of hexane. The acetonitrile layer was concentrated in vacuo and the resulting solid was suspended in 10 mL of ethyl ether, filtered and dried in vacuo at 60° C. to afford 0.2 g (89%) of the title compound.
Reaction SMILES: [Cl-].[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[C:9]([CH2:16][P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:8]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[C:7]2[C:41]1[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([O:49][CH3:50])[CH:42]=1.[O-]CC.[Na+].[CH:55]([C:57]1[N:58]([CH3:62])[CH:59]=[CH:60][N:61]=1)=O.O>C(O)C>[CH3:2][O:3][C:4]1[CH:5]=[C:6]2[C:11](=[CH:12][C:13]=1[O:14][CH3:15])[N:10]=[C:9](/[CH:16]=[CH:55]/[C:57]1[N:58]([CH3:62])[CH:59]=[CH:60][N:61]=1)[C:8]([C:36]([O:38][CH2:39][CH3:40])=[O:37])=[C:7]2[C:41]1[CH:46]=[CH:45][C:44]([O:47][CH3:48])=[C:43]([O:49][CH3:50])[CH:42]=1
Reactant: CCOC(=O)c1c(C[P+](c2ccccc2)(c2ccccc2)c2ccccc2)nc2cc(OC)c(OC)cc2c1-c1ccc(OC)c(OC)c1
Reactant: Cn1ccnc1C=O
Agent: CC[O-]
Agent: [Cl-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)c1c(/C=C/c2nccn2C)nc2cc(OC)c(OC)cc2c1-c1ccc(OC)c(OC)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 67.1 %

Procedure:
[6,7-Dimethoxy-4-(3,4-dimethoxyphenyl)-3-ethoxycarbonylquinolin-2-yl]methyltriphenylphosphonium chloride (17.4 g) was added at room temperature to a solution of sodium ethoxide in ethanol (prepared from Na (0.62 g) and ethanol (150 ml)). Then a solution of 2-formyl-1-methylimidazole (3.7 g) in ethanol (20 ml) was added dropwise. The mixture was stirred at room temperature for 3 hours, poured into water and extracted with ethyl acetate. The ethyl acetate layer was washed with water and dried over magnesium sulfate, and the solvent was evaporated. The residue was subjected to column chromatography on silica gel. The fractions eluted with chloroform/methanol (100/1, v/v) gave ethyl (E)-6,7-dimethoxy-4-(3,4-dimethoxyphenyl)-2-[2-(1-methylimidazol-2-yl)vinyl]quinoline-3-carboxylate (8.3 g, 67%) which was then recrystallized from ethyl acetate.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:29])[CH:5]=[CH:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([O:23][CH3:24])=[C:16]([O:25][CH3:26])[C:15]=2[O:27][CH3:28])=[CH:9][CH:8]=1)[CH3:2].[H][H]>C(O)C.[Pd].[C]>[CH2:1]([O:3][C:4](=[O:29])[CH2:5][CH2:6][C:7]1[CH:12]=[CH:11][C:10]([CH2:13][C:14]2[C:19]([CH3:20])=[C:18]([O:21][CH3:22])[C:17]([O:23][CH3:24])=[C:16]([O:25][CH3:26])[C:15]=2[O:27][CH3:28])=[CH:9][CH:8]=1)[CH3:2]
Reactant: [H][H]
Reactant: CCOC(=O)C=Cc1ccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)cc1
Agent: [Pd]
Solvent: CCO
Product: CCOC(=O)CCc1ccc(Cc2c(C)c(OC)c(OC)c(OC)c2OC)cc1
Yield: 85 %

Procedure:
The compound (1.07 g, 2.67 mmol) obtained in step 4 was dissolved in ethanol (100 ml) and 5% Pd-carbon (200 mg) was added thereto, which was then stirred under a stream of hydrogen at room temperature for 16 hours. The reaction mixture was filtered and the filtrate was concentrated to yield the title compound (914 mg, 2.27 mmol, yield 85%).
Reaction SMILES: [CH2:1]([N:3]([CH2:19][CH3:20])[CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]([N+:13]([O-])=O)=[C:9]([N+:16]([O-])=O)[CH:8]=1)[CH3:2].[O:21]1[CH2:26][CH2:25][N:24]([C:27]2[CH:32]=[CH:31][C:30]([NH:33][C:34]([C:36]3[CH:43]=[CH:42][C:39]([CH:40]=O)=[CH:38][CH:37]=3)=[O:35])=[CH:29][CH:28]=2)[CH2:23][CH2:22]1>>[CH2:1]([N:3]([CH2:19][CH3:20])[CH2:4][CH2:5][O:6][C:7]1[CH:12]=[CH:11][C:10]2[N:13]=[C:40]([C:39]3[CH:38]=[CH:37][C:36]([C:34]([NH:33][C:30]4[CH:29]=[CH:28][C:27]([N:24]5[CH2:23][CH2:22][O:21][CH2:26][CH2:25]5)=[CH:32][CH:31]=4)=[O:35])=[CH:43][CH:42]=3)[NH:16][C:9]=2[CH:8]=1)[CH3:2]
Reactant: CCN(CC)CCOc1ccc([N+](=O)[O-])c([N+](=O)[O-])c1
Reactant: O=Cc1ccc(C(=O)Nc2ccc(N3CCOCC3)cc2)cc1
Product: CCN(CC)CCOc1ccc2nc(-c3ccc(C(=O)Nc4ccc(N5CCOCC5)cc4)cc3)[nH]c2c1

Procedure:
Compound 643 was prepared according to the procedure similar to that described in Scheme III from 1-(2-diethylaminoethyloxy)-3,4-dinitrobenzene and 4-(4-(4-morpholinophenyl)aminocarbonylbenzaldehyde. [M+H]+ calcd for C30H35N5O3: 514.27; found: 514.13.
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[NH:8][N:9]=[C:10]([OH:11])[C:5]2=[C:4]([CH3:12])[CH:3]=1.[N:13]([CH2:16][CH2:17][C:18]1[S:19][CH:20]=[CH:21][CH:22]=1)=[C:14]=[O:15]>C1COCC1>[S:19]1[CH:20]=[CH:21][CH:22]=[C:18]1[CH2:17][CH2:16][NH:13][C:14]([N:9]1[C:10](=[O:11])[C:5]2[C:6](=[N:7][C:2]([Cl:1])=[CH:3][C:4]=2[CH3:12])[NH:8]1)=[O:15]
Reactant: Cc1cc(Cl)nc2[nH]nc(O)c12
Reactant: O=C=NCCc1cccs1
Solvent: C1CCOC1
Product: Cc1cc(Cl)nc2[nH]n(C(=O)NCCc3cccs3)c(=O)c12

Procedure:
In analogy to example 1c, 200 mg (1.09 mmol) of 6-chloro-4-methyl-1H-pyrazolo-[3,4-b]pyridin-3-ol were reacted with 183.5 mg (1.19 mmol) of 2-(2-isocyanatoethyl)-thiophene in THF at room temperature. Yield: 184 mg (50%), M+H+: 337.09.
Reaction SMILES: F[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9].[NH2:11][CH2:12][CH2:13][C:14]([CH3:17])([OH:16])[CH3:15].C(N(CC)CC)C>C1COCC1>[CH3:15][C:14]([OH:16])([CH2:13][CH2:12][NH:11][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N+:8]([O-:10])=[O:9])[CH3:17]
Reactant: CC(C)(O)CCN
Reactant: O=[N+]([O-])c1ccccc1F
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CC(C)(O)CCNc1ccccc1[N+](=O)[O-]
Yield: 83.2 %

Procedure:
A solution of 1-fluoro-2-nitrobenzene (1.9 mL, 18 mmol), 4-amino-2-methyl-2-butanol (1.6 g, 15 mmol) and triethylamine (6.4 mL, 46 mmol) in THF (30 mL) was refluxed for 8 h. Then the reaction was quenched by addition of water (50 mL) and extracted with ethyl acetate (50 mL×2). The combined organic layers were washed with brine (50 mL) and dried over sodium sulfate, filtered and concentrated. The residue was purified by column chromatography on silica gel eluting with hexane/ethyl acetate (5/1-2/1) to afford 2.8 g (82%) of the title compound.
Reaction SMILES: [Br:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=O)=[CH:4][C:3]=1[O:11][CH2:12][CH2:13][C:14]1[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=1.C1C=CC2N(O)N=NC=2C=1.Cl.[CH3:32][O:33][C:34]([C:36]1([NH2:45])[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37]1)=[O:35].C(Cl)CCl>CN(C=O)C>[CH3:32][O:33][C:34]([C:36]1([NH:45][C:6](=[O:8])[C:5]2[CH:9]=[CH:10][C:2]([Br:1])=[C:3]([O:11][CH2:12][CH2:13][C:14]3[CH:15]=[C:16]([CH3:20])[CH:17]=[CH:18][CH:19]=3)[CH:4]=2)[CH2:44][C:43]2[C:38](=[CH:39][CH:40]=[CH:41][CH:42]=2)[CH2:37]1)=[O:35]
Reactant: Cc1cccc(CCOc2cc(C(=O)O)ccc2Br)c1
Reactant: COC(=O)C1(N)Cc2ccccc2C1
Agent: Cl
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CN(C)C=O
Product: COC(=O)C1(NC(=O)c2ccc(Br)c(OCCc3cccc(C)c3)c2)Cc2ccccc2C1
Reaction time: 8 h
Yield: 90.3 %

Procedure:
The compound of step 2 (0.410 g, 1.22 mmol) was dissolved in DMF (5 ml), EDIA (0.790 g, 6.12 mmol), HOBT (33 mg, 0.244 mmol), and 2-amino-indane-2-carboxylic acid methyl ester hydrochloride (0.246 g, 1.47 mmol) were added, the mixture was cooled in an ice bath and EDC (352 mg, 1.84 mmol) was added. The mixture was stirred overnight. The volatiles were evaporated in vacuo, the mixture was partitioned between 2 N hydrochloric acid and EA, the organic phase was dried over magnesium sulfate and evaporated to dryness. The residue was purified by silica gel chromatography (HEP/EA gradient) to give 0.56 g of the title compound.
Reaction SMILES: [C:1]([N:5]1[CH:9]=[C:8]([CH2:10][CH2:11][CH2:12][CH3:13])[C:7](=[NH:14])[S:6]1)([CH3:4])([CH3:3])[CH3:2].[CH3:15][O:16][C:17]([CH:19]1[CH2:23][CH2:22][C:21]([CH3:27])([C:24](O)=[O:25])[C:20]1([CH3:29])[CH3:28])=[O:18].C(N(CC)CC)C>C(#N)C>[CH2:10]([C:8]1=[CH:9][N:5]([C:1]([CH3:4])([CH3:3])[CH3:2])[S:6]/[C:7]/1=[N:14]\[C:24]([C:21]1([CH3:27])[CH2:22][CH2:23][CH:19]([C:17]([O:16][CH3:15])=[O:18])[C:20]1([CH3:29])[CH3:28])=[O:25])[CH2:11][CH2:12][CH3:13]
Reactant: COC(=O)C1CCC(C)(C(=O)O)C1(C)C
Reactant: CCCCc1cn(C(C)(C)C)sc1=N
Solvent: CC#N
Solvent: CCN(CC)CC
Product: CCCCc1cn(C(C)(C)C)s/c1=N\C(=O)C1(C)CCC(C(=O)OC)C1(C)C
Temperature: 60 °C

Procedure:
To a 20-mL scintillation vial containing a magnetic stir bar were added the product from Example 92B (637 mg, 3.00 mmol), racemic 3-(methoxycarbonyl)-1,2,2-trimethylcyclopentanecarboxylic acid (Maybridge, 771 mg, 3.60 mmol), and 2-(1H-benzo[d][1,2,3]triazol-1-yl)-1,1,3,3-tetramethylisouronium tetrafluoroborate (TBTU, Bachem, 1.16 g, 3.60 mmol). Anhydrous acetonitrile (8 mL) was added to form a white slurry. Neat triethylamine (Aldrich, 1.09 g, 10.8 mmol) was added via syringe to form a tan solution. The reaction flask was heated to 60° C. in a shaker block and mixed for 2 hours. The volatiles were removed by rotary evaporator to give a brown oil. The product was purified by flash chromatography (silica gel: 2-20% ethyl acetate in hexanes) to afford the title compound. 1H NMR (DMSO-d6) δ 0.50 (s, 3H), 0.90 (t, J=7.5 Hz, 3H), 1.21 (s, 3H), 1.24-1.36 (m, 2H), 1.30 (s, 3H), 1.41-1.51 (m, 1H), 1.57 (s, 9H), 1.57-1.67 (m, 2H), 1.73-1.87 (m, 1H), 2.01-2.11 (m, 1H), 2.62-2.67 (m, 2H), 2.70-2.81 (m, 1H), 2.85-2.91 (m, 1H), 3.60 (s, 3H), 8.50 (s, 1H). MS (ESI+) m/z 409 (M+H)+. Anal. calcd. for C22H36N2O3S: C, 64.67; H, 8.88; N, 6.86. Found: C, 64.20; H, 8.71; N, 6.59.
Reaction SMILES: Cl[C:2]1[CH:3]=[CH:4][C:5]2[C:6]([N:11]=1)=[N:7][CH:8]=[CH:9][N:10]=2.[CH:12]([Sn](CCCC)(CCCC)CCCC)=[CH2:13]>C1COCC1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH:12]([C:2]1[CH:3]=[CH:4][C:5]2[C:6]([N:11]=1)=[N:7][CH:8]=[CH:9][N:10]=2)=[CH2:13]
Reactant: Clc1ccc2nccnc2n1
Reactant: C=C[Sn](CCCC)(CCCC)CCCC
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C=Cc1ccc2nccnc2n1
Temperature: 65 °C
Reaction time: 3 h
Yield: 80.8 %

Procedure:
6-chloropyrido[2,3-b]pyrazine (Intermediate 4.2) (3 g, 18.12 mmol, 1.00 eq.) was dissolved in THF (150 mL) and degassed with nitrogen at rt for 10 minutes. Tetrakis (triphenylphosphine) palladium(0) (1.46 g, 1.27 mmol, 0.07 eq.) and vinyltributylstannane (7.47 mL, 23.5 mmol, 1.3 eq.) were added and reaction mixture was stirred at 65° C. for 3 hours. THF was evaporated and crude purified directly by flash chromatography using cyclohexane/ethyl acetate (8/2) to give 2.3 g of the expected compound (Intermediate 4.3) as an orange oil. Amount: 2.3 g; Yield: 81%; Formula: C9H7N3; HPLC Purity: 98%; HPLC H2O TFA 0.1%-ACN TFA 0.05%): Rt (min); Area %=1.32 min; 98%; 1H NMR (DMSO-d6) δ 9.10 (s, 1H), 8.98 (s, 1H), 8.46 (d, 1H, J=8 Hz), 7.95 (d, 1H, J=8 Hz), 6.90 (dd, 1H, Jtrans=17 Hz, Jcis=10 Hz), 6.50 (dd, 1H, Jtrans=17 Hz, Jgem=1.5 Hz), 5.80 (dd, 1H, Jcis=10 Hz, Jgem=1.5 Hz). LC-MS: M/Z ESI: Rt (min) 0.78 min, 158.13 (M+1).
Reaction SMILES: [Br:1][C:2]1[C:22]([OH:23])=[CH:21][C:5]2[C:6]([C:9]([C:11]3[CH:16]=[C:15]([F:17])[C:14]([O:18][CH3:19])=[C:13]([F:20])[CH:12]=3)=[O:10])=[CH:7][O:8][C:4]=2[C:3]=1[Br:24].[N+]([O-])(O)=[O:26].O>CC(O)=O>[Br:1][C:2]1[C:22](=[O:23])[C:21](=[O:26])[C:5]2[C:6]([C:9](=[O:10])[C:11]3[CH:16]=[C:15]([F:17])[C:14]([O:18][CH3:19])=[C:13]([F:20])[CH:12]=3)=[CH:7][O:8][C:4]=2[C:3]=1[Br:24]
Reactant: O=[N+]([O-])O
Reactant: COc1c(F)cc(C(=O)c2coc3c(Br)c(Br)c(O)cc23)cc1F
Solvent: O
Solvent: CC(=O)O
Product: COc1c(F)cc(C(=O)c2coc3c2C(=O)C(=O)C(Br)=C3Br)cc1F
Temperature: 60 °C
Yield: 90.5 %

Procedure:
To a solution of (6,7-dibromo-5-hydroxybenzofuran-3-yl)(3,5-difluoro-4-methoxyphenyl)methanone (30 mg, 0.065 mmol) in AcOH (1 mL) was added nitric acid—69% (20.03 μl, 0.325 mmol) at room temperature. The mixture was heated to 60° C. for 3 hours, cooled to room temperature, poured onto iced water and the suspension filtered. A red/orange solid was isolated which was dried under vacuum to afford the product (28 mg, 91%).
Reaction SMILES: C([O:3][C:4](=[O:30])[CH2:5][CH2:6][S:7][C:8]1[S:12][C:11]([NH:13][C:14]([N:16]([CH:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)=[O:15])=[N:10][C:9]=1[CH3:29])C.C(OC(=O)CCSC1SC(N)=NC=1C)C>>[CH:23]1([N:16]([CH:17]2[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]2)[C:14](=[O:15])[NH:13][C:11]2[S:12][C:8]([S:7][CH2:6][CH2:5][C:4]([OH:30])=[O:3])=[C:9]([CH3:29])[N:10]=2)[CH2:24][CH2:25][CH2:26][CH2:27][CH2:28]1
Reactant: CCOC(=O)CCSc1sc(NC(=O)N(C2CCCCC2)C2CCCCC2)nc1C
Agent: CCOC(=O)CCSc1sc(N)nc1C
Product: Cc1nc(NC(=O)N(C2CCCCC2)C2CCCCC2)sc1SCCC(=O)O

Procedure:
Prepared as described in general procedures (A) and (B) using 3-[2-(3,3-dicyclohexyl-ureido)-4-methyl-thiazol-5-ylsulfanyl]-propionic acid ethyl ester and 3-(2-amino-4-methyl-thiazol-5-ylsulfanyl)-propionic acid ethyl ester
Reaction SMILES: [CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13](Cl)=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:18][CH2:19][CH:20]([OH:29])[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28].C(N(CC)CC)C>C(Cl)Cl>[CH2:1]([O:8][C:9]1[CH:17]=[CH:16][C:12]([C:13]([O:29][CH:20]([CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH3:28])[CH2:19][F:18])=[O:14])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(Cl)c1ccc(OCc2ccccc2)cc1
Reactant: CCCCCCCCC(O)CF
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCC(CF)OC(=O)c1ccc(OCc2ccccc2)cc1
Temperature: 0 °C
Reaction time: 12 h
Yield: 38.3 %

Procedure:
To a solution of 4-benzyloxybenzoic acid chloride (1.3 g) in methylene chloride (25 ml) was slowly added under ice cooling a solution of optically active 1-monofluoro-2-decanol (1.0g, [α]D20 =-7.2) and triethylamine (0.5 g) in methylene chloride (25 ml). The mixture was left to stand until it reached room temperature and stirred for 12 hours. The mixture was poured in ice water and extracted with methylene chloride. The extracted layer was washed with dilute aqueous hydrochloric acid solution, water, 1N aqueous sodium carbonate solution and water, in this order, and dehydrated over anhydrous magnesium sulfate. The solution was distilled under reduced pressure to remove the solvent until a crude product was obtained. The product was subjected to silica-gel column chromatography to obtain 1-monofluoro-2-decyl 4-benzyloxybenzoate (0.78 g). The benzoate and 10% palladium carried on carbon (0.13 g) were added to ethanol and then subjected to de-benzylation under a hydrogen atmosphere to obtain 1-monofluoro-2-decyl-4-hydroxybenzoate (0.6 g).
Reaction SMILES: [C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:12]2[N:13]=[CH:14][N:15]=[CH:16][C:11]=2[C:10](Br)=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].C([Sn](CCCC)(CCCC)[C:24]([O:26]CC)=[CH2:25])CCC.O>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:12]2[N:13]=[CH:14][N:15]=[CH:16][C:11]=2[C:10]([C:24](=[O:26])[CH3:25])=[CH:9]1)([CH3:4])([CH3:3])[CH3:2]
Reactant: CC(C)(C)OC(=O)Cn1cc(Br)c2cncnc21
Reactant: C=C(OCC)[Sn](CCCC)(CCCC)CCCC
Agent: [Pd]
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: O
Solvent: Cc1ccccc1
Product: CC(=O)c1cn(CC(=O)OC(C)(C)C)c2ncncc12
Temperature: 25 °C

Procedure:
A solution of (5-bromo-pyrrolo[2,3-d]pyrimidin-7-yl)-acetic acid tert-butyl ester (220 mg, 0.71 mmol), tri-butyl(1-ethoxyvinyl)tin (285 μL, 0.85 mmol) and tetrakis(triphenylphosphine) palladium (16.28 mg, 14.1 μmol) in toluene (7 mL) was heated at 110° C. for 72 h under argon atmosphere. The mixture was allowed to cool to RT, poured into water and extracted with EtOAc (×2). The combined organic layers were dried (Na2SO4), filtered and concentrated. The crude residue was purified by flash column chromatography on silica gel (CH2Cl2 to CH2Cl2/MeOH 94:6). TLC, Rf (CH2Cl2/MeOH 9:1)=0.54; MS (UPLC/MS): 276.3 [M+H]+, 320.4 [M+HCOO]−; tR (HPLC conditions f): 1.40 min.
Reaction SMILES: [N:1]([CH2:4][C@@H:5]1[O:9][C:8](=[O:10])[N:7]([C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[C:19](=[O:25])[CH2:18]3)=[C:13]([F:26])[CH:12]=2)[CH2:6]1)=[N+]=[N-].[C:27](OCC)(=[O:29])[CH3:28]>CN(C=O)C>[F:26][C:13]1[CH:12]=[C:11]([N:7]2[CH2:6][C@H:5]([CH2:4][NH:1][C:27](=[O:29])[CH3:28])[O:9][C:8]2=[O:10])[CH:16]=[CH:15][C:14]=1[N:17]1[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[C:19](=[O:25])[CH2:18]1
Reactant: CCN1CCN(c2ccc(N3C[C@H](CN=[N+]=[N-])OC3=O)cc2F)CC1=O
Reactant: CCOC(C)=O
Solvent: CN(C)C=O
Product: CCN1CCN(c2ccc(N3C[C@H](CNC(C)=O)OC3=O)cc2F)CC1=O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
(5R)-5-Azidomethyl-3-(3-fluoro-4-{4-ethyl-3-oxopiperazin-1-yl-}phenyl)oxazolidin-2-one (750 mg) was dissolved in a mixture of DMF (5 ml) and ethyl acetate (10 ml), and the solution purged with argon. Palladium (10% on carbon, 150 mg) was added, followed by acetic anhydride (0.4 ml) and the mixture stirred at ambient temperature under hydrogen confined in a balloon for 2 hours. The mixture was filtered through celite, evaporated to dryness, and chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 10% methanol in dichloromethane. Relevant fractions were combined and evaporated, and the residue purified by crystallisation from acetonitrile to give N-(5S)-[3-(3-fluoro-4-{4-ethyl-3-oxopiperazin-1-yl}phenyl)-2-oxooxazolidin-5-ylmethyl]acetamide (145 mg).
Reaction SMILES: [NH:1]([C:8]1[CH:16]=[C:15]([C:17](O)=[O:18])[C:14]([NH:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[CH:13][C:9]=1[C:10](O)=[O:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C1C=CC2[C@]3(C)[C@@H](CCC=2C=1)[C@@](CN)(C)CCC3)C.[OH-].[K+]>O.C(O)(=O)C>[CH:24]1[CH:25]=[C:26]2[C:17]([C:15]3[C:14]([NH:20][C:21]2=[CH:22][CH:23]=1)=[CH:13][C:9]1[C:10]([C:7]2[C:2]([NH:1][C:8]=1[CH:16]=3)=[CH:3][CH:4]=[CH:5][CH:6]=2)=[O:11])=[O:18]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: CC(C)c1ccc2c(c1)CC[C@H]1[C@](C)(CN)CCC[C@]21C
Agent: [K+]
Agent: [OH-]
Solvent: CC(=O)O
Solvent: O
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 0 °C
Yield: 96 %

Procedure:
100 parts of 2,5-dianilinoterephthalic acid are added with stirring at 100°-120° C. to 450 parts of polyphosphoric acid (P2O5 content 85.5%), the mixture is stirred at said temperature until the reaction has ended (which takes about 2 hours) and is then poured onto 1,350 parts of ice-water, and the hydrolysis suspension attains a temperature of 15°-20° C. After the hydrolysis has ended the precipitated crude quinacridone is filtered off and is washed with water until free of acid. The water-moist approximately 20-22% strength crude quinacridone thus obtained is suspended in 600 parts of water. A solution of 1.2 parts of dehydroabietylamine, 10.6 parts of water and 0.24 part of acetic acid is then added dropwise, and the mixture is stirred for 30 minutes. 150 parts of 10% strength aqueous potassium hydroxide solution are then added, and the mixture is bulked with water to a total of 1,500 parts. The suspension is then refluxed with stirring for 10 hours and is then filtered at 70°-80° C., and the filter cake is washed with water until neutral. The water-moist approximately 18-22% strength quinacridone thus isolated is suspended in 600 parts of 80% strength isobutanol, and the suspension is then stirred at 145°-150° C. in a sealed vessel for 5 hours. The isobutanol is then distilled off with steam, and the pigment is then filtered off, is washed with water and is dried at 80° C. The pigment yield is at least 96%.
Reaction SMILES: [NH2:1][C:2]1[CH:29]=[C:28]([N:30]([CH2:32][CH2:33][CH2:34][N:35]([CH3:37])[CH3:36])[CH3:31])[CH:27]=[CH:26][C:3]=1[C:4]([NH:6][C:7]1[C:15]2[C:10](=[CH:11][CH:12]=[C:13]([O:16][CH2:17][C:18]3[CH:23]=[C:22]([F:24])[CH:21]=[C:20]([F:25])[CH:19]=3)[CH:14]=2)[NH:9][N:8]=1)=[O:5].[O:38]1[CH2:43][CH2:42][C:41](=O)[CH2:40][CH2:39]1.C(O)(C(F)(F)F)=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.C[N+](C)(C)C>C(Cl)Cl>[F:24][C:22]1[CH:23]=[C:18]([CH:19]=[C:20]([F:25])[CH:21]=1)[CH2:17][O:16][C:13]1[CH:14]=[C:15]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[C:7]2[NH:6][C:4](=[O:5])[C:3]1[CH:26]=[CH:27][C:28]([N:30]([CH2:32][CH2:33][CH2:34][N:35]([CH3:36])[CH3:37])[CH3:31])=[CH:29][C:2]=1[NH:1][CH:41]1[CH2:42][CH2:43][O:38][CH2:39][CH2:40]1
Reactant: O=C1CCOCC1
Reactant: CN(C)CCCN(C)c1ccc(C(=O)Nc2n[nH]c3ccc(OCc4cc(F)cc(F)c4)cc23)c(N)c1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: C[N+](C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CN(C)CCCN(C)c1ccc(C(=O)Nc2n[nH]c3ccc(OCc4cc(F)cc(F)c4)cc23)c(NC2CCOCC2)c1
Yield: 46.5 %

Procedure:
2-Amino-N-[5-(3,5-difluoro-benzyloxy)-1H-indazol-3-yl]-4-[(3-dimethylamino-propyl)-methyl-amino]-benzamide (150 mg, 0.29 mmol) in DCM (4 mL) was treated, at 4° C., under a nitrogen atmosphere, with tetrahydro-4H-pyran-4-one (0.34 mL, 0.37 mmol), TFA (0.23 mL, 2.95 mmol) and finally with tetramethylammonium triacetoxyborohydride ((204 mg, 0.74 mmol). After 1.5 hours DCM, was added (25 mL) and the organic layer was washed with water (25 mL), saturated NaHCO3 solution (25 mL) and brine. After drying over anhydrous sodium sulfate, removal of the solvent and purification of the crude over silica gel (DCM: 7N NH3 in MeOH 9:1), 80 mg of title compound were obtained in 46% yield.
Reaction SMILES: [CH3:1][C@@:2]12[C@H:11]3[CH2:12][CH2:13][C@:14]4([CH3:25])[C:18]([C:19]5[CH:20]=[CH:21][CH:22]=[N:23][CH:24]=5)=[CH:17][CH2:16][C@H:15]4[C@@H:10]3[CH2:9][CH:8]=[C:7]1[CH2:6][C@@H:5]([OH:26])[CH2:4][CH2:3]2.[C:27](OC(=O)C)(=[O:29])[CH3:28].C(N(CC)CC)C>C(Cl)Cl>[CH3:28][C:27]([O:26][C@@H:5]1[CH2:6][C:7]2[C@@:2]([CH3:1])([C@@H:11]3[C@@H:10]([CH2:9][CH:8]=2)[C@@H:15]2[CH2:16][CH:17]=[C:18]([C:19]4[CH:20]=[CH:21][CH:22]=[N:23][CH:24]=4)[C@@:14]2([CH3:25])[CH2:13][CH2:12]3)[CH2:3][CH2:4]1)=[O:29]
Reactant: CC(=O)OC(C)=O
Reactant: C[C@]12CC[C@H](O)CC1=CC[C@@H]1[C@@H]2CC[C@]2(C)C(c3cccnc3)=CC[C@@H]12
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(=O)O[C@H]1CC[C@@]2(C)C(=CC[C@@H]3[C@@H]2CC[C@]2(C)C(c4cccnc4)=CC[C@@H]32)C1
Temperature: -2.5 °C
Reaction time: 25 h

Procedure:
The crude abiraterone thus obtained (about 64 g) is taken up in methylene chloride (350 mL), and the resulting mixture, cooled to a temperature of −5 to 0° C., is added with acetic anhydride (130 mL) and then with triethylamine (190 mL), maintaining the temperature at −5 to 0° C. The mixture is stirred at room temperature for about 25 h, then washed with water and concentrated under vacuum, taking up the residue in acetone (250 mL). The resulting solid is isolated by filtration (at 0-5° C.) and dried under vacuum at 40° C. for 16 h (about 46 g; purity: 82.5%; assay: about 73%). A second fraction of crude abiraterone acetate, as an oil, is obtained by concentration of the mother liquor under vacuum (54 g, purity: 74%, assay: about 45%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[N:11][C:12](Cl)=[CH:13][C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[CH:5][CH:4]=1.[C:24]1([SH:30])[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[N:11][C:12]([S:30][C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)=[CH:13][C:14]=2[C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)=[CH:5][CH:4]=1
Reactant: Sc1ccccc1
Reactant: COc1ccc(-c2cc(Cl)nnc2-c2ccc(OC)cc2)cc1
Product: COc1ccc(-c2cc(Sc3ccccc3)nnc2-c2ccc(OC)cc2)cc1

Procedure:
In a similar manner as in Example 2, 3,4-bis(4-methoxyphenyl)-6-chloropyridazine (352.5 mg, 1.08 mmol) and thiophenol were reacted as starting materials at 100° C. for 7 hours and post-treatment was then conducted, whereby the title compound was obtained as a colorless crystalline powder (55.8 mg, 12.9%). Melting point: 176.9-177.8° C. (chloroform-diethyl ether)