Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[C:7]1([C:13](B(O)O)=[CH2:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[O:18]1[CH2:23][CH2:22][CH2:21][O:20][CH:19]1[C:24]1[CH:29]=[CH:28][C:27]([C:30]2[S:31][C:32]3[CH:38]=[C:37](Br)[CH:36]=[CH:35][C:33]=3[N:34]=2)=[C:26]([F:40])[CH:25]=1>O1CCOCC1.CO>[O:18]1[CH2:23][CH2:22][CH2:21][O:20][CH:19]1[C:24]1[CH:29]=[CH:28][C:27]([C:30]2[S:31][C:32]3[CH:38]=[C:37]([C:13]([C:7]4[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=4)=[CH2:14])[CH:36]=[CH:35][C:33]=3[N:34]=2)=[C:26]([F:40])[CH:25]=1
Reactant: C=C(B(O)O)c1ccccc1
Reactant: Fc1cc(C2OCCCO2)ccc1-c1nc2ccc(Br)cc2s1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: CO
Product: C=C(c1ccccc1)c1ccc2nc(-c3ccc(C4OCCCO4)cc3F)sc2c1
Temperature: 90 °C

Procedure:
A slurry of (amphos)2PdCl2 (0.114 g, 0.161 mmol), potassium carbonate (2.85 g, 20.6 mmol), 1-phenylvinylboronic acid (2.10 g, 14.2 mmol), 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-6-bromobenzo[d]thiazole (2.54 g, 6.44 mmol) in 20 mL dioxane/4 mL water was flushed with argon and sealed, and heated at 90° C. overnight. In the morning the reaction mixture was cooled and judged complete by LCMS. The reaction mixture was partitioned between EA/H2O and the organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to give a solid. The material was suspended in MeOH, and filtered. The resulting solid was dried in vacuo to give 2-(4-(1,3-dioxan-2-yl)-2-fluorophenyl)-6-(1-phenylvinyl)benzo[d]thiazole as a dull yellow solid. MS (ESI) m/z: Calculated: 417.1; Observed: 418.0 (M++1).
Reaction SMILES: Br[CH2:2][C:3]([C:5]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:17][CH:18]1[CH2:20][CH2:19]1)[C:9]([CH3:16])=[N:10]2)=[O:4].[C:21]([O:25][C:26]([NH:28][C@@H:29]([C@H:38]([O:40][Si:41]([C:44]([CH3:47])([CH3:46])[CH3:45])([CH3:43])[CH3:42])[CH3:39])[C:30](=[O:37])[CH2:31][C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])([CH3:24])([CH3:23])[CH3:22].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[C:21]([O:25][C:26]([NH:28][C@@H:29]([C@H:38]([O:40][Si:41]([C:44]([CH3:46])([CH3:45])[CH3:47])([CH3:42])[CH3:43])[CH3:39])[C:30](=[O:37])[CH:31]([CH2:2][C:3]([C:5]1[C:14]([F:15])=[CH:13][CH:12]=[C:11]2[C:6]=1[N:7]=[C:8]([NH:17][CH:18]1[CH2:20][CH2:19]1)[C:9]([CH3:16])=[N:10]2)=[O:4])[C:32]([O:34][CH2:35][CH3:36])=[O:33])=[O:27])([CH3:24])([CH3:22])[CH3:23]
Reactant: CCOC(=O)CC(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)O[Si](C)(C)C(C)(C)C
Reactant: Cc1nc2ccc(F)c(C(=O)CBr)c2nc1NC1CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCOC(=O)C(CC(=O)c1c(F)ccc2nc(C)c(NC3CC3)nc12)C(=O)[C@@H](NC(=O)OC(C)(C)C)[C@@H](C)O[Si](C)(C)C(C)(C)C
Temperature: 25 °C
Reaction time: 16 h
Yield: 22.3 %

Procedure:
A solution of 2-bromo-1-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)ethanone (613) (566 mg, 1.674 mmol) and (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-3-oxohexanoate (614) (995 mg, 2.465 mmol) in DMF (9 mL) was cooled in an ice-water bath and treated with K2CO3 (509 mg, 3.68 mmol) The mixture was stirred for 16 h at RT then heated at 60° C. in an oil bath for 4 h. The mixture was extracted into CHCl3 (3×100 mL) from saturated aq. NaHCO3 (100 mL), dried (Na2SO4), concentrated, and purified by flash chromatography on silica gel (40 g) eluting with a gradient of 0-10% EtOAc in DCM to give (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate (352a) (247 mg, 0.374 mmol, 22% yield) as a yellow foam. LC-MS m/z 661.1, [M+H]. A solution of (4S,5R)-ethyl 4-((tert-butoxycarbonyl)amino)-5-((tert-butyldimethylsilyl)oxy)-2-(2-(3-(cyclopropylamino)-6-fluoro-2-methylquinoxalin-5-yl)-2-oxoethyl)-3-oxohexanoate (352a) (247 mg, 0.374 mmol) in EtOH (3.0 mL) and AcOH (1.5 mL) was treated with NH4OAc (Aldrich) (432 mg, 5.61 mmol). The resulting yellow solution was heated at 60° C. for 64 h. The mixture was concentrated and extracted into EtOAc (3×100 mL) from saturated aq. NaHCO3 (150 mL). The organic extracts were dried (Na2SO4), concentrated, and purified by flash chromatography on silica gel (gradient: 0-15% EtOAc in DCM) to give the title compound (352b) as a yellow foam (184.5 mg). LC-MS m/z 642.2, [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]2[N:17]([C:18]3[CH:23]=[CH:22][C:21]([C:24]4([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:34])([CH3:33])[CH3:32])[CH2:27][CH2:26][CH2:25]4)=[CH:20][CH:19]=3)[C:11]3=[N:12][C:13](Cl)=[CH:14][CH:15]=[C:10]3[N:9]=2)=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)(O)[O-].[Na+].[C:41]([NH:44][C:45]1[CH:46]=[C:47](B(O)O)[CH:48]=[CH:49][CH:50]=1)(=[O:43])[CH3:42]>C1(C)C=CC=CC=1.C(O)C>[C:41]([NH:44][C:45]1[CH:50]=[C:49]([C:13]2[N:12]=[C:11]3[N:17]([C:18]4[CH:19]=[CH:20][C:21]([C:24]5([NH:28][C:29](=[O:35])[O:30][C:31]([CH3:32])([CH3:34])[CH3:33])[CH2:27][CH2:26][CH2:25]5)=[CH:22][CH:23]=4)[C:8]([C:7]4[C:2]([NH2:1])=[N:3][CH:4]=[CH:5][CH:6]=4)=[N:9][C:10]3=[CH:15][CH:14]=2)[CH:48]=[CH:47][CH:46]=1)(=[O:43])[CH3:42]
Reactant: CC(=O)Nc1cccc(B(O)O)c1
Reactant: CC(C)(C)OC(=O)NC1(c2ccc(-n3c(-c4cccnc4N)nc4ccc(Cl)nc43)cc2)CCC1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CCO
Product: CC(=O)Nc1cccc(-c2ccc3nc(-c4cccnc4N)n(-c4ccc(C5(NC(=O)OC(C)(C)C)CCC5)cc4)c3n2)c1
Temperature: 100 °C

Procedure:
To a suspension of tert-butyl (1-(4-(2-(2-aminopyridin-3-yl)-5-chloro-3H-imidazo[4,5-b]pyridin-3-yl)phenyl)cyclobutyl)carbamate (3.0 g) in toluene (100 mL) and ethanol (100 mL) was added saturated aqueous sodium bicarbonate (15 ml) and (3-acetamidophenyl) boronic acid (2.18 g). The reaction was degassed for 5 minutes and Pd(PPh3)4 (0.300 g) was added. The reaction was again degassed for 5 minutes with nitrogen and then heated to 100° C. overnight. The reaction mixture was cooled to room temperature, dichloromethane (250 ml) and water (100 ml) were added to the reaction. The organics were separated, the aqueous washed with dichloromethane (1×100 ml) and the organics combined. The organics were washed with saturated sodium bicarbonate (1×100 ml) and brine (1×100 ml). The organics were dried over sodium sulfate and concentrated under reduced pressure. Purification by column chromatography (0-10% methanol in dichloromethane) gave the product as a brown solid with some co-eluting impurities. The fractions with the product were combined and concentrated to give a dark brown solid. The solid was triturated with ethyl acetate to give a tan solid (2.6 g, 70%). 400 M Hz 1H NMR (DMSO-d6) δ: 10.08 (s, 1H), 8.28 (d, J=8.0 Hz, 1H), 8.11 (bs, 1H), 7.99 (dd, J=5.2 Hz and 2.0 Hz, 1H), 7.84 (d, J=8.4 Hz, 1H), 7.72-7.63 (m, 3H), 7.55-7.51 (m, 2H), 7.46-7.42 (m, 6H), 7.39-7.34 (m, 1H), 7.14-7.06 (m, 1H), 7.02 (s, 2H), 6.32 (dd, J=7.6 Hz and 4.8 Hz 1H), 2.48-2.40 (m, 4H), 2.07-1.98 (m, 4H), 1.89-1.79 (m, 1H), 1.38-1.12 (m, 9H); LCMS: 590 [M+H].
Reaction SMILES: [CH2:1]([N:4]([CH2:13][CH:14]=[CH2:15])[CH:5]=[CH:6][CH:7]=[C:8]([C:11]#[N:12])[C:9]#[N:10])[CH:2]=[CH2:3].C(N)C=C.C(N)(=[O:23])C=C.NC=CC=C(C#N)C#N>C(O)C.Cl.CC(C)=O>[C:9]([NH2:10])(=[O:23])[C:8]([CH3:11])=[CH2:7].[CH2:1]([N:4]([CH:5]=[CH:6][CH:7]=[C:8]([C:9]#[N:10])[C:11]#[N:12])[CH2:13][CH:14]=[CH2:15])[CH:2]=[CH2:3]
Reactant: C=CC(N)=O
Agent: C=CCN(C=CC=C(C#N)C#N)CC=C
Agent: Cl
Agent: N#CC(C#N)=CC=CN
Solvent: CCO
Solvent: C=CCN
Solvent: CC(C)=O
Product: C=C(C)C(N)=O
Temperature: 90 °C
Reaction time: 20 h

Procedure:
40 g of intermediate (A) and 10.6 g of allylamine in 580 ml of ethanol and 19.6 ml of 37% hydrochloric acid were dissolved in a flask provided with a stirrer and reflux condenser. Under stirring and raising the mixture temperature up to 90° C., a solution of 107.7 g of acrylamide and 4.2 g of 2.2'-azobisisobutyrronitrile in 648 ml of ethanol was added thereto. The reaction mixture was kept at 90° C. for 20 hours and then poured into 2 liters of acetone; the precipitated product was grinded and washed upon decantation with one liter of acetone, filtered and dried. 108.6 g of a water soluble product were obtained, containing about 10% w/w of aminoallylidenmalononitrile moieties.
Reaction SMILES: [Br:1][C:2]1[N:3]=[C:4]([C:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[NH:9][N:8]=2)[S:5][CH:6]=1.[H-].[Na+].Cl[C:19]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)([C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>CN(C=O)C>[Br:1][C:2]1[N:3]=[C:4]([C:7]2[C:15]3[C:10](=[N:11][CH:12]=[CH:13][CH:14]=3)[N:9]([C:19]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)([C:32]3[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=3)[C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[N:8]=2)[S:5][CH:6]=1
Reactant: Brc1csc(-c2n[nH]c3ncccc23)n1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: Brc1csc(-c2nn(C(c3ccccc3)(c3ccccc3)c3ccccc3)c3ncccc23)n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A solution of 3-(4-bromothiazol-2-yl)-1H-pyrazolo[5,4-b]pyridine (161 mg, 0.5727 mmol) in DMF (3 mL) was cooled to 0° C. then sodium hydride (27.49 mg, 0.6872 mmol) was added in one portion. Stirred at 0° C. for 30 mins before (chloro-diphenyl-methyl)benzene (167.6 mg, 0.6013 mmol) was added. Ice-bath removed and stirred at room temperature for 2 h. Quenched with water, diluted with EtOAc. Organic layer then collected, washed with brine, dried (MgSO4), filtered and concentrated in vacuo.
Reaction SMILES: [CH:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([S:14]([NH:17][C:18]3C=CC=CC=3)(=[O:16])=[O:15])=[CH:10][C:9]=2[N+:24]([O-:26])=[O:25])=[CH:3][CH:2]=1.C1C(N)=[C:31]2[C:34](C3C(O)=CC(Br)=C(N)C=3C(=O)C2=C(O)C=1)=[O:35].[CH:48]1C=CC(NC2C=CC([OH2+])=C3C(C4C(C(=O)C=23)=C([N+]([O-])=O)C=CC=4[O-])=O)=CC=1>>[CH3:31][CH2:34][O:35][C:1]1[CH:6]=[CH:5][C:4]([NH:7][C:8]2[CH:13]=[CH:12][C:11]([S:14]([N:17]([CH3:48])[CH3:18])(=[O:16])=[O:15])=[CH:10][C:9]=2[N+:24]([O-:26])=[O:25])=[CH:3][CH:2]=1
Reactant: O=[N+]([O-])c1cc(S(=O)(=O)Nc2ccccc2)ccc1Nc1ccccc1
Reactant: Nc1ccc(O)c2c1C(=O)c1c(O)cc(Br)c(N)c1C2=O
Reactant: O=C1c2c([O-])ccc([N+](=O)[O-])c2C(=O)c2c(Nc3ccccc3)ccc([OH2+])c21
Product: CCOc1ccc(Nc2ccc(S(=O)(=O)N(C)C)cc2[N+](=O)[O-])cc1

Procedure:
0.185 % C.I. Disperse Yellow 42; 0.122 % C.I. Disperse Red 91; 0.05 % C.I. Disperse Blue 56; 0.44 % C.I. Disperse Blue 77; and 3.5 % of the dispersion of the dispersion of Example 11 above.
Reaction SMILES: [O:1]1[CH2:7][CH2:6][CH2:5][O:4][C:3]2[CH:8]=[C:9](B(O)O)[CH:10]=[CH:11][C:2]1=2.Cl[C:16]1[C:25]([N:26]([CH:28]([CH3:30])[CH3:29])[CH3:27])=[N:24][C:23]2[C:18](=[CH:19][CH:20]=[C:21]([C:31]([O:33][CH3:34])=[O:32])[CH:22]=2)[N:17]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.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>[O:1]1[CH2:7][CH2:6][CH2:5][O:4][C:3]2[CH:8]=[C:9]([C:16]3[C:25]([N:26]([CH:28]([CH3:30])[CH3:29])[CH3:27])=[N:24][C:23]4[C:18](=[CH:19][CH:20]=[C:21]([C:31]([O:33][CH3:34])=[O:32])[CH:22]=4)[N:17]=3)[CH:10]=[CH:11][C:2]1=2
Reactant: OB(O)c1ccc2c(c1)OCCCO2
Reactant: COC(=O)c1ccc2nc(Cl)c(N(C)C(C)C)nc2c1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: C1COCCO1
Solvent: O
Product: COC(=O)c1ccc2nc(-c3ccc4c(c3)OCCCO4)c(N(C)C(C)C)nc2c1
Temperature: 90 °C
Reaction time: 1 h
Yield: 63 %

Procedure:
To a solution of 3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-ylboronic acid (200.0 mg, 1.03 mmol in dioxane (5.0 mL) was added methyl 2-chloro-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate (Scheme I, 150.0 mg, 0.52 mmol), K3PO4 (325.9 mg, 1.54 mmol) and Pd(PPh3)4 (29.7 mg, 0.03 mmol) and water (3 drops) with stirring for 1 h at 90° C. in an oil bath maintained with an inert atmosphere of nitrogen. The reaction mixture was concentrated under vacuum to give a residue, which was purified by a silica gel column with 1% ethyl acetate in petroleum ether to afford methyl 2-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-3-(isopropyl(methyl)amino)quinoxaline-6-carboxylate as a light yellow solid (140.0 mg, 63%).
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[NH:13][N:12]=[N:11][N:10]=1.[C:14]([O:18][C:19]([N:21]1[CH2:25][C@H:24](OS(C2C=CC(C)=CC=2)(=O)=O)[CH2:23][C@H:22]1[C:37](N1CCN(C2C=CC=CC=2C#N)CC1)=[O:38])=[O:20])([CH3:17])([CH3:16])[CH3:15].[C:53](=O)([O-])[O-:54].[Na+].[Na+]>CN(C=O)C.CC(=O)OCC>[CH3:53][O:54][C:37]([C@@H:22]1[CH2:23][C@H:24]([N:11]2[N:12]=[N:13][C:9]([C:3]3[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=3[F:1])=[N:10]2)[CH2:25][N:21]1[C:19]([O:18][C:14]([CH3:15])([CH3:16])[CH3:17])=[O:20])=[O:38]
Reactant: Fc1ccc(-c2nnn[nH]2)c(F)c1
Reactant: Cc1ccc(S(=O)(=O)O[C@@H]2C[C@@H](C(=O)N3CCN(c4ccccc4C#N)CC3)N(C(=O)OC(C)(C)C)C2)cc1
Reactant: O=C([O-])[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOC(C)=O
Product: COC(=O)[C@@H]1C[C@H](n2nnc(-c3ccc(F)cc3F)n2)CN1C(=O)OC(C)(C)C
Reaction time: 8 h
Yield: 61.8 %

Procedure:
To a solution of (2,4-difluoro-phenyl)-tetrazole (0.44 g, 1.1 mmol) in 5 ml DMF was added 0.1 g (0.55 mmol) of (2S,4R)-2-[4-(2-cyano-phenyl)-piperazine-1-carbonyl]-4-(toluene-4-sulfonyloxy)-pyrrolidine-1-carboxylic acid tert-butyl ester and anhydrous sodium carbonate (0.15 g, 1.4 mmol). The mixture was stirred vigorously at 60 degree overnight. The solution was diluted with 30 ml EA and washed with 1M Na2CO3, 5% citric acid and brine, dried and concentrated to give the crude product as yellow oil (0.14 g, 0.34 mmol). MS m/e=410.3 [M+H]+.
Reaction SMILES: [CH3:1][C:2]1[C:6]2[C:7](=[O:19])[N:8]([CH2:11][CH2:12][N:13]3[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]3)[CH2:9][CH2:10][C:5]=2[NH:4][C:3]=1[CH:20]=O.[Cl:22][C:23]1[C:24]([F:39])=[C:25]([C:29]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:30]=2[CH2:31][C:32](=[O:38])[NH:33]3)[CH:26]=[CH:27][CH:28]=1>>[Cl:22][C:23]1[C:24]([F:39])=[C:25]([C:29]2[CH:37]=[CH:36][CH:35]=[C:34]3[C:30]=2[C:31](=[CH:20][C:3]2[NH:4][C:5]4[CH2:10][CH2:9][N:8]([CH2:11][CH2:12][N:13]5[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18]5)[C:7](=[O:19])[C:6]=4[C:2]=2[CH3:1])[C:32](=[O:38])[NH:33]3)[CH:26]=[CH:27][CH:28]=1
Reactant: Cc1c(C=O)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Reactant: O=C1Cc2c(cccc2-c2cccc(Cl)c2F)N1
Product: Cc1c(C=C2C(=O)Nc3cccc(-c4cccc(Cl)c4F)c32)[nH]c2c1C(=O)N(CCN1CCCCC1)CC2
Yield: 53.1 %

Procedure:
The title compound was prepared under the same conditions as described in Example 25 with 3-methyl-4-oxo-5-(2-piperidin-1-yl-ethyl)-4,5,6,7-tetrahydro-1H-pyrrolo[3,2-c]pyridine-2-carbaldehyde and 4-(3-chloro-2-fluoro-phenyl)-1,3-dihydro-indol-2-one (prepared according to WO2002055517) as starting materials to give 2-[4-(3-chloro-2-fluoro-phenyl)-2-oxo-1,2-dihydro-indol-3-ylidenemethyl]-3-methyl-5-(2-piperidin-1-yl-ethyl)-1,5,6,7-tetrahydro-pyrrolo[3,2-c]pyridin-4-one (40 mg, 53.1%) as an orange solid.
Reaction SMILES: Br[C:2]1[S:6][C:5]([C:7]2[S:8][C:9](Br)=[CH:10][CH:11]=2)=[CH:4][CH:3]=1.[Si:13]([O:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]1[CH:32]=[CH:31][C:30](B2OC(C)(C)C(C)(C)O2)=[CH:29][CH:28]=1)([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14].[C:42](=[O:45])([O-])[O-].[K+].[K+]>C1COCC1.O.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>[Si:13]([O:45][CH2:42][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][C:27]1[CH:28]=[CH:29][C:30]([C:2]2[S:6][C:5]([C:7]3[S:8][C:9]([C:30]4[CH:29]=[CH:28][C:27]([CH2:26][CH2:25][CH2:24][CH2:23][CH2:22][CH2:21][O:20][Si:13]([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:14])[CH3:15])=[CH:32][CH:31]=4)=[CH:10][CH:11]=3)=[CH:4][CH:3]=2)=[CH:31][CH:32]=1)([C:16]([CH3:17])([CH3:18])[CH3:19])([CH3:15])[CH3:14]
Reactant: O=C([O-])[O-]
Reactant: CC1(C)OB(c2ccc(CCCCCCO[Si](C)(C)C(C)(C)C)cc2)OC1(C)C
Reactant: Brc1ccc(-c2ccc(Br)s2)s1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: [K+]
Solvent: C1CCOC1
Solvent: O
Product: CC(C)(C)[Si](C)(C)OCCCCCCc1ccc(-c2ccc(-c3ccc(-c4ccc(CCCCCCO[Si](C)(C)C(C)(C)C)cc4)s3)s2)cc1
Reaction time: 0.33 h
Yield: 62.9 %

Procedure:
To a stirred solution of 5,5′-dibromo-[2,2′]bithiophene (0.60 g, 1.85 mmol) in anhydrous THF (50 ml) is added tetrakis(triphenylphosphine)palladium(0) (0.10 g) under N2, with stirring. After 20 min, 2-{4-[6-(tert-butyl-dimethylsilanyloxy)hexyl]-phenyl}-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (2.30 g, 5.50 mmol) and a solution of potassium carbonate (1.50 g) in water (10 ml) is added. This mixture is heated at reflux for 2 h. After cooling, water is added and the mixture is extracted with ethyl acetate (3×50 ml). The extracts are dried (Na2SO4) and evaporated under reduced pressure. The residue is purified by column chromatography on silica, eluting with petroleum ether/ethyl acetate (from 10:0 to 4:1), to give a yellow solid (0.87 g, 64%). 1H NMR (300 MHz, CDCl3): δ(ppm) 7.52 (d, J=8.1 Hz, 4H, Ar—H), 7.13-7.20 (m, 8H, Ar—H), 3.60 (t, J=6.4 Hz, 4H, OCH2), 2.62 (t, J=7.3 Hz, 4H, Ar—CH2), 1.35-1.65 (m, 16H, CH2), 0.89 (s, 18H, CH3), 0.05 (s, 12H, CH3); 13C NMR (75 MHz, CDCl3): δ(ppm) 143.2 (2×quat.), 142.5 (2×quat.), 136.3 (2×quat.), 131.5 (2×quat.), 129.0 (4×CH), 125.5 (4×CH), 124.3 (2×CH), 123.3 (2×CH), 63.3 (2×OCH2), 35.6 (2×CH2), 32.8 (2×CH2), 31.4 (2×CH2), 29.1 (2×CH2), 26.0 (3×CH3), 25.7 (CH2), 18.4 (2×quat.), −5.2 (2×CH3). HRMS 746.4080 (calc. for C44H66O2S2Si2 746.4043).
Reaction SMILES: [C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)(=[O:3])[CH3:2].[Br:10]Br>Br>[BrH:10].[Br:10][CH2:2][C:1]([C:4]1[CH:5]=[N:6][CH:7]=[CH:8][CH:9]=1)=[O:3]
Reactant: CC(=O)c1cccnc1
Reactant: BrBr
Agent: Br
Product: O=C(CBr)c1cccnc1
Temperature: 70 °C

Procedure:
To 10 g (82.5 mmol) of 3-acetylpyridine was added 30 ml of 48% hydrobromic acid. The reaction mixture was heated to 70° C., and 4.2 ml of bromine was added dropwise with stirring. After completed addition of bromine, the reaction mixture was stirred further for 15 minutes at the same temperature and cooled on ice. A crystalline compound formed was filtered off and thoroughly washed with acetone. This yields 21 g (90%) of 3-bromoacetylpyridine hydrobromide, melting point 195-200° C.
Reaction SMILES: I(O)(O)(O)(O)(O)=[O:2].[OH:8][C@@H:9]1[C@H:25]2[C@@H:16]([CH2:17][CH2:18][C:19]3[C@:24]2([CH3:26])[CH2:23][CH2:22][C:21](=[O:27])[CH:20]=3)[C@H:15]2[C@@:11]([CH3:33])([C@@:12]([OH:32])([C:28](=[O:31])CO)[CH2:13][CH2:14]2)[CH2:10]1>O.C1COCC1.[OH-].[Na+]>[OH:8][C@@H:9]1[C@H:25]2[C@@H:16]([CH2:17][CH2:18][C:19]3[C@:24]2([CH3:26])[CH2:23][CH2:22][C:21](=[O:27])[CH:20]=3)[C@H:15]2[C@@:11]([CH3:33])([C@@:12]([OH:32])([C:28]([OH:2])=[O:31])[CH2:13][CH2:14]2)[CH2:10]1
Reactant: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)CO
Reactant: [O-][I+](O)(O)(O)(O)O
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: C1CCOC1
Product: C[C@]12CCC(=O)C=C1CC[C@@H]1[C@@H]2[C@@H](O)C[C@@]2(C)[C@H]1CC[C@]2(O)C(=O)O
Temperature: 25 °C
Reaction time: 2 h
Yield: 94.9 %

Procedure:
A solution of orthoperiodic acid (21.4 g, 94 mmol) in water (80 ml) was added to a solution of (8S,9S,10R,11S,13S,14S,17R)-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,9,10,11,12,13,14,15,16,17-dodecahydro-1H-cyclopenta[a]phenanthren-3(2H)-one (Hydrocortisone, 17.0 g, 46.9 mmol) in THF (350 ml), and the reaction mixture was stirred at room temperature in an open flask for 2 hours. Then the mixture was poured onto ice. After the ice had molten, the mixture was extracted with ethyl acetate (3 times 150 ml). Evaporation of the solvent gave a white solid, which was dissolved in aqueous NaOH (1 M, 150 ml). The solution was washed with ethyl acetate, and acidified with conc. aqueous HCl. The precipitate formed was collected by filtration, and dried on the sinter overnight to afford the target compound as an off-white powder (15.51 g, 95%).
Reaction SMILES: [C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][Cl:20])[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH2:21][CH2:22][CH3:23])[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[CH3:24][N:25]1[C:29]([CH3:30])=[N:28][N:27]=[C:26]1[SH:31]>>[ClH:20].[C:1]([C:5]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][CH2:18][CH2:19][S:31][C:26]3[N:25]([CH3:24])[C:29]([CH3:30])=[N:28][N:27]=3)[CH2:13][CH2:12]2)[CH:8]=[C:7]([CH2:21][CH2:22][CH3:23])[N:6]=1)([CH3:4])([CH3:3])[CH3:2]
Reactant: Cc1nnc(S)n1C
Reactant: CCCc1cc(N2CCN(CCCCl)CC2)nc(C(C)(C)C)n1
Product: CCCc1cc(N2CCN(CCCSc3nnc(C)n3C)CC2)nc(C(C)(C)C)n1
Product: Cl
Yield: 36.2 %

Procedure:
Reaction of 1 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-propyl-pyrimidine (2.95 mmol) with 0.42 g of 4-methyl-5-methyl-4H-[1,2,4]triazole-3-thiol (3.25 mmol) yielded 0.5 g (33.6%) of title compound as a solid.
Reaction SMILES: [CH2:1]([N:3]([CH2:26][CH3:27])[CH2:4][CH2:5][NH:6][C:7]1[C:20]2[C:19](=[O:21])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:22][CH3:23])[CH:17]=3)[S:12][C:11]=2[C:10]([CH:24]=O)=[CH:9][CH:8]=1)[CH3:2].[CH:28]([NH2:30])=[O:29].[OH-].[Na+]>>[CH2:1]([N:3]([CH2:26][CH3:27])[CH2:4][CH2:5][NH:6][C:7]1[C:20]2[C:19](=[O:21])[C:18]3[C:13](=[CH:14][CH:15]=[C:16]([O:22][CH3:23])[CH:17]=3)[S:12][C:11]=2[C:10]([CH2:24][NH:30][CH:28]=[O:29])=[CH:9][CH:8]=1)[CH3:2]
Reactant: NC=O
Reactant: CCN(CC)CCNc1ccc(C=O)c2sc3ccc(OC)cc3c(=O)c12
Agent: [Na+]
Agent: [OH-]
Product: CCN(CC)CCNc1ccc(CNC=O)c2sc3ccc(OC)cc3c(=O)c12
Temperature: 170 °C

Procedure:
A mixture of 1-[[2-(diethylamino)ethyl]amino]-7-methoxy-9-oxothioxanthen-4-carboxaldehyde (3.6 g, 0. 0094 mol), formamide (48 mL) nd formic acid (6 mL) was heated to 170° C. under N2 for 8 hours. The mixture was poured into ice-water, basified with 35% NaOH and extracted with chloroform. The organic layer was separated, washed with water (2×), then brine and was dried over Na2SO4 and concentrated in vacuo to afford 3.88 g of N-[[1-[[2-(diethylamino) ethyl]amino]-7-methoxy-9-oxothioxanthen-4-yl]-methyl ]formamide.
Reaction SMILES: [NH2:1][C:2]1[C:3]([C:9]([O:11]C)=[O:10])=[N:4][C:5](Br)=[CH:6][N:7]=1.[F:13][C:14]1[CH:15]=[C:16](B(O)O)[CH:17]=[CH:18][CH:19]=1.C([O-])([O-])=O.[K+].[K+]>CC#N.CO.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[NH2:1][C:2]1[C:3]([C:9]([OH:11])=[O:10])=[N:4][C:5]([C:18]2[CH:17]=[CH:16][CH:15]=[C:14]([F:13])[CH:19]=2)=[CH:6][N:7]=1
Reactant: OB(O)c1cccc(F)c1
Reactant: COC(=O)c1nc(Br)cnc1N
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC#N
Solvent: O
Solvent: CO
Product: Nc1ncc(-c2cccc(F)c2)nc1C(=O)O
Yield: 82.3 %

Procedure:
Methyl 3-amino-6-bromopyrazine-2-carboxylate (0.116 g, 0.5 mmol), 3-fluorophenylboronic acid (0.14 g, 1.0 mmol), dichlorobis(triphenylphosphine)palladium(II) (0.018 g, 0.02 mmol), and K2CO3 (0.14 g, 1.0 mmol) were combined in 3 mL of 4:1 CH3CN:H2O and heated to 150° C. for 10 minutes in the SmithSynthesizer microwave. Upon cooling, the reaction mixture was diluted with MeOH and H2O to dissolve all but the catalyst. The mixture was filtered and the pH was adjusted to 6 with 2N HCl. The solution was concentrated in vacuo, and the solids were collected to afford 3-amino-6-(3-fluorophenyl)pyrazine-2-carboxylic acid (96 mg) as a yellow solid.