Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:22]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][N:23]=2)=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:20])([CH3:19])[CH3:18])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.[B-](F)(F)(F)[F:31].[B-](F)(F)(F)F.C1[N+]2(CCl)CC[N+](F)(CC2)C1>C(#N)C>[Cl:1][C:2]1[C:3]([C:22]2[C:27]([CH3:28])=[CH:26][C:25]([CH3:29])=[CH:24][N:23]=2)=[C:4]([F:31])[C:5]([N:8]2[CH2:9][CH2:10][CH:11]([NH:14][C:15](=[O:21])[O:16][C:17]([CH3:18])([CH3:19])[CH3:20])[CH2:12][CH2:13]2)=[N:6][CH:7]=1
Reactant: Cc1cnc(-c2cc(N3CCC(NC(=O)OC(C)(C)C)CC3)ncc2Cl)c(C)c1
Reactant: F[B-](F)(F)F
Agent: F[N+]12CC[N+](CCl)(CC1)CC2
Solvent: CC#N
Product: Cc1cnc(-c2c(Cl)cnc(N3CCC(NC(=O)OC(C)(C)C)CC3)c2F)c(C)c1
Temperature: 0 °C
Reaction time: 2 h
Yield: 29 %

Procedure:
A cooled (0° C.), stirred suspension of tert-butyl (1-(5′-chloro-3,5-dimethyl-[2,4′-bipyridin]-2′-yl)piperidin-4-yl)carbamate (550 mg, 1.32 mmol) in acetonitrile (13 mL) was treated with Selectfluor® (827 mg, 2.24 mmol) portionwise. A light yellow solution was obtained and stirring was continued for 2 h. LC-MS showed the reaction was ˜70% complete. The reaction was quenched with water at this point to avoid more by-product formation. EtOAc was added and layers were separated. The aqueous layer was extracted with EtOAc (2×). The organic extract was dried over sodium sulfate and concentrated to give the crude product, which was purified on ISCO separation system with a 12-gram column using 0-40% EtOAc in heptane to afford 164 mg (29%) of white foam: LRMS (M+H)+: 435.1; 1H NMR (400 MHz, CDCl3) δ 1.43-1.50 (m, 11 H), 2.03 (d, J=12.13 Hz, 2 H), 2.14 (s, 3 H), 2.39 (s, 3 H), 2.90-3.12 (m, 2 H), 3.69 (br. s., 1 H), 3.87-4.08 (m, 2 H), 4.48 (br. s., 1 H), 7.46 (s, 1 H), 8.09 (s, 1 H), 8.40 (s, 1 H).
Reaction SMILES: C(O)=O.Cl[S:5]([N:8]=C=O)(=[O:7])=[O:6].[NH2:11][C:12]1[N:13]=[C:14]([Cl:37])[C:15]2[C:20]([C:21]#[C:22][CH2:23][CH2:24][OH:25])=[CH:19][N:18]([CH2:26][C:27]3[C:32]([CH3:33])=[C:31]([O:34][CH3:35])[C:30]([CH3:36])=[CH:29][N:28]=3)[C:16]=2[N:17]=1>CN(C)C(=O)C.C(Cl)Cl>[S:5](=[O:6])(=[O:7])([O:25][CH2:24][CH2:23][C:22]#[C:21][C:20]1[C:15]2[C:14]([Cl:37])=[N:13][C:12]([NH2:11])=[N:17][C:16]=2[N:18]([CH2:26][C:27]2[C:32]([CH3:33])=[C:31]([O:34][CH3:35])[C:30]([CH3:36])=[CH:29][N:28]=2)[CH:19]=1)[NH2:8]
Reactant: COc1c(C)cnc(Cn2cc(C#CCCO)c3c(Cl)nc(N)nc32)c1C
Reactant: O=C=NS(=O)(=O)Cl
Solvent: ClCCl
Solvent: O=CO
Solvent: CC(=O)N(C)C
Product: COc1c(C)cnc(Cn2cc(C#CCCOS(N)(=O)=O)c3c(Cl)nc(N)nc32)c1C
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of formic acid (0.463 g) and N,N-dimethylacetamide (1 drop) was added to a solution of chlorosulfonyl isocyanate (1.31 g) in DCM (9 mL), and heated to reflux for 3 h. The resulting solution was added to a solution of 4-[2-Amino-4-chloro-7-(4-methoxy-3,5-dimethyl-pyridin-2-ylmethyl)-7H-pyrrolo[2,3-d]pyrimidin-5-yl]-but-3-yn-1-ol (see example 2) (200 mg) in DMA (10 mL) and stirred at rt for 30 min. Work-up and reverse-phase preparative HPLC gave the title compound, as a solid. HPLC Rt=4.96 min.
Reaction SMILES: [CH3:1][C:2]([CH3:7])=[CH:3][C:4]([OH:6])=[O:5].[N-:8]=[N+:9]=[N-:10].[Na+]>C(O)(=O)C.O>[N:8]([C:2]([CH3:7])([CH3:1])[CH2:3][C:4]([OH:6])=[O:5])=[N+:9]=[N-:10]
Reactant: CC(C)=CC(=O)O
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: O
Solvent: CC(=O)O
Product: CC(C)(CC(=O)O)N=[N+]=[N-]
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a stirred solution of 3,3-dimethylacrylic acid (20 g, 0.2 mol) in glacial acetic acid (50 mL) was added a solution of sodium azide (52 g, 0.8 mol) in water (100 mL) in one portion. The clear yellow solution was stirred for 1 hour at room temperature and then heated in an oil bath at 95° C. for 2 days. Water (50 mL) was added to the cooled orange solution. This solution was poured into a separatory funnel and extracted with ether (5×200 mL). The combined organic extracts were dried over anhydrous MgSO4 and concentrated to an orange oil. This oil was used without further purification. 1H NMR (CDCl3, 400 MHz): δ 1.44 (s, 6H), 2.55 (s, 2H), 11.80 (bs, 1H).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[CH2:7][N:8](C(OCC)=O)[CH2:9][CH2:10][C:2]=12.O.[OH-].[K+]>CO.[Cl-].[Na+].O>[N:1]1[CH:6]=[CH:5][N:4]=[C:3]2[CH2:7][NH:8][CH2:9][CH2:10][C:2]=12
Reactant: CCOC(=O)N1CCc2nccnc2C1
Agent: [Cl-]
Agent: [K+]
Agent: [Na+]
Solvent: CO
Solvent: O
Product: c1cnc2c(n1)CCNC2
Temperature: 65 °C
Reaction time: 4 h

Procedure:
To a solution of ethyl 7,8-dihydropyrido[3,4-b]pyrazine-6(5H)-carboxylate (150 mg, 0.724 mmol) in MeOH (20 mL)/H2O (2 mL) is added KOH (500 mg, 8.91 mmol). The mixture is stirred overnight at rt and 4 hr at 65° C. The reaction mixture is cooled, and brine (50 mL) is added. The solution is extracted with DCM (3×100 mL). The combined organic extracts are dried and evaporated to yield the title compound. MS (+VE) m/z 136.20 (M++1).
Reaction SMILES: [N+:1]([C:4]1[CH:5]=[C:6]([C:10]2[N:11]=[C:12]([CH2:15][N:16]3[CH:20]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:18]=[N:17]3)[S:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1)([O-])=O>C(O)C.O1CCCC1.[Pd]>[NH2:1][C:4]1[CH:5]=[C:6]([C:10]2[N:11]=[C:12]([CH2:15][N:16]3[CH:20]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[CH:18]=[N:17]3)[S:13][CH:14]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: CCOC(=O)c1cnn(Cc2nc(-c3cccc([N+](=O)[O-])c3)cs2)c1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)c1cnn(Cc2nc(-c3cccc(N)c3)cs2)c1
Temperature: 25 °C
Reaction time: 3 h
Yield: 100.4 %

Procedure:
To a mixed solution of the compound (3.15 g, 8.8 mmol) obtained in Example 25a in ethanol-tetrahydrofuran (v/v=1/1, 18 ml) was added Pd—C (10% wet., 320 mg), and the mixture was stirred at room temperature for 3 hr under a hydrogen atmosphere. Pd—C was removed, and the solvent was evaporated under reduced pressure to give a crude title compound (2.9 g).
Reaction SMILES: FC(F)(F)C(O)=O.COC([C@@H]1C[C@H](N=[N+]=[N-])CN1)=O.[CH3:20][O:21][C:22]([C@@H:24]1[CH2:28][C@H:27]([NH2:29])[CH2:26][N:25]1[CH2:30][CH:31]1[CH2:36][CH2:35][CH2:34][CH2:33][CH2:32]1)=[O:23]>>[CH3:20][O:21][C:22]([C@@H:24]1[CH2:28][C@H:27]([NH2:29])[CH2:26][N:25]1[CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:23]
Reactant: COC(=O)[C@@H]1C[C@H](N)CN1CC1CCCCC1
Agent: COC(=O)[C@@H]1C[C@H](N=[N+]=[N-])CN1
Solvent: O=C(O)C(F)(F)F
Product: COC(=O)[C@@H]1C[C@H](N)CN1Cc1ccccc1

Procedure:
(2S,4S)-4-Amino-1-benzyl-pyrrolidine-2-carboxylic acid methyl ester was prepared from (2S,4S)-4-azido-pyrrolidine-2-carboxylic acid methyl ester trifluoroacetate salt in a similar reaction sequence used in the preparation of (2S,4S)-4-amino-1-cyclohexylmethyl-pyrrolidine-2-carboxylic acid methyl ester. MS calcd. for C13H19N2O2 [(M+H)+] 235, obsd. 235.
Reaction SMILES: [CH3:1][CH:2]1[C:11](=[O:12])[CH2:10][CH2:9][C:4]2([O:8][CH2:7][CH2:6][O:5]2)[CH2:3]1.CCC(C)[BH-](C(C)CC)C(C)CC.[K+].[OH-].[Na+].OO>O1CCCC1>[CH3:1][C@H:2]1[C@@H:11]([OH:12])[CH2:10][CH2:9][C:4]2([O:5][CH2:6][CH2:7][O:8]2)[CH2:3]1
Reactant: CC1CC2(CCC1=O)OCCO2
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: OO
Agent: [K+]
Solvent: C1CCOC1
Product: C[C@@H]1CC2(CC[C@@H]1O)OCCO2
Temperature: 0 °C
Reaction time: 1 h
Yield: 85.1 %

Procedure:
To a tetrahydrofuran (100 mL) solution of 7-methyl-1,4-dioxa-spiro[4.5]-decan-8-one (Tetrahedron Asymmetry 2001, 12, 1683) (9.50 g), K-Selectride (1.0 mol/L tetrahydrofuran solution, 65 mL) was gradually added at −78° C. After 1 hour, the reaction mixture was warmed to 0° C., and a 1 N aqueous sodium hydroxide solution (120 mL) and 30% aqueous hydrogen peroxide (100 mL) were gradually added thereto. The purified aqueous mixture was stirred overnight, followed by two extractions with dichloromethane. The organic layer was washed with saturated brine, then dried over sodium sulfate, and then concentrated. The residue was purified by chromatography (hexane/ethyl acetate=4:1→2:1→1:1) to obtain the title compound (8.18 g, 85%) as a colorless oil.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[CH2:5][NH:6][C:7]1[C:12]([C:13](Cl)=[O:14])=[C:11]([Cl:16])[N:10]=[C:9]([S:17][CH3:18])[N:8]=1.C(Cl)Cl.[CH2:27]([O:34][CH2:35][CH2:36][OH:37])[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C(=O)([O-])O.[Na+]>O>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[CH2:5][NH:6][C:7]1[C:12]([C:13]([O:37][CH2:36][CH2:35][O:34][CH2:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)=[O:14])=[C:11]([Cl:16])[N:10]=[C:9]([S:17][CH3:18])[N:8]=1
Reactant: OCCOCc1ccccc1
Reactant: COc1ccc(CNc2nc(SC)nc(Cl)c2C(=O)Cl)cc1Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: COc1ccc(CNc2nc(SC)nc(Cl)c2C(=O)OCCOCc2ccccc2)cc1Cl

Procedure:
A mixture of whole amount of 4-(3-chloro-4-methoxybenzylamino)-5-chloroformyl-6-chloro-2-methylthiopyrimidine (prepared in the above (1)), methylene chloride 15 ml and 2-benzyloxyethanol 224 mg is refluxed for 30 minutes. After cooling the reaction mixture is diluted with water and neutralized with an aqueous saturated sodium hydrogen carbonate solution. The solution is washed with ethyl acetate. The methylene chloride layer is diluted with ethyl acetate, washed, dried and concentrated in vacuo. The residue is separated with silica gel chromatography (solvent; hexane:ethyl acetate=5:1) to give 4-(3-chloro-4-methoxybenzylamino)-5-(2-benzyloxyethoxycarbonyl)-6-chloro-2-methylthiopyrimidine as a colorless oil 655 mg.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2([C:12]([N:14]3[CH2:18][CH2:17][C@@:16]4([C:22]5[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=5[C:20](=[O:27])[O:19]4)[CH2:15]3)=[O:13])[CH2:11][CH2:10][CH2:9]2)=[CH:4][CH:3]=1.[O:28]1[CH2:32][CH2:31][NH:30][C:29]1=[O:33].C1(C)C=CC=CC=1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[O:33]=[C:29]1[N:30]([C:2]2[CH:7]=[CH:6][C:5]([C:8]3([C:12]([N:14]4[CH2:18][CH2:17][C@@:16]5([C:22]6[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=6[C:20](=[O:27])[O:19]5)[CH2:15]4)=[O:13])[CH2:11][CH2:10][CH2:9]3)=[CH:4][CH:3]=2)[CH2:31][CH2:32][O:28]1
Reactant: O=C1NCCO1
Reactant: O=C1O[C@]2(CCN(C(=O)C3(c4ccc(Br)cc4)CCC3)C2)c2ccccc21
Agent: [Pd]
Agent: CC(C)(C)P(C(C)(C)C)C(C)(C)C
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Solvent: Cc1ccccc1
Product: O=C1O[C@]2(CCN(C(=O)C3(c4ccc(N5CCOC5=O)cc4)CCC3)C2)c2ccccc21
Temperature: 50 °C

Procedure:
To a solution of (1R)-1′-{[1-(4-bromophenyl)cyclobutyl]carbonyl}-3H-spiro[2-benzofuran-1,3′-pyrrolidin]-3-one (20.7 mg, 0.0000485 mol) and oxazolidin-2-one (12.7 mg, 0.000146 mol) in freshly distilled toluene (0.34 mL, 0.0032 mol), were added tris(dibenzylidene acetone)dipalladium(0) (4.4 mg, 0.0000048 mol), tri-tert-butylphosphine (2.0 mg, 0.0000097 mol) and cesium carbonate (15.8 mg, 0.0000485 mol), and the mixture was heated to 50° C. overnight. The reaction mixture then was cooled to rt, filtered over celite and concentrated under reduced pressure. The crude product was purified by prep-HPLC. LC/MS (M+H) 433.2.
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4](Cl)=[O:5].[CH3:12][C:13]1[CH:14]=[C:15]([O:19][CH3:20])[CH:16]=[CH:17][CH:18]=1.C1(C)C=CC=CC=1>[Fe](Cl)(Cl)Cl.O>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Cl:11])[C:3]=1[C:4]([C:18]1[CH:17]=[CH:16][C:15]([O:19][CH3:20])=[CH:14][C:13]=1[CH3:12])=[O:5]
Reactant: O=C(Cl)c1c(Cl)cccc1Cl
Reactant: COc1cccc(C)c1
Agent: Cl[Fe](Cl)Cl
Solvent: Cc1ccccc1
Solvent: O
Product: COc1ccc(C(=O)c2c(Cl)cccc2Cl)c(C)c1
Temperature: 100 °C

Procedure:
A mixture of 2,6-dichlorobenzoylchloride (5.24 g; 25 mmol), 3-methylanisole (2.44 g; 20 mmol) and iron(III)chloride (20 mg) is heated to 100° C. for 45 minutes with stirring. After cooling, toluene is added, the mixture is shaken with water, the organic phase is dried and the solvent is evaporated. The reaction product is purified chromatograpically (flash column with 70 g of silicagel; elution with petrolether/toluene changing from 75:25 to 40:60 (v/v)). After evaporation the residue from the main fraction is treated with petrolether to give white crystalls (1.33 g; 22.5% y); mp. 89° C.
Reaction SMILES: [C:1]1([CH2:7][C:8]([NH:10][C@H:11]([C:13]([OH:15])=O)[CH3:12])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl.[NH2:17][C@@H:18]([CH2:23][CH2:24][CH3:25])[C:19]([O:21][CH3:22])=[O:20]>>[C:1]1([CH2:7][C:8]([NH:10][C@H:11]([C:13]([NH:17][C@@H:18]([CH2:23][CH2:24][CH3:25])[C:19]([O:21][CH3:22])=[O:20])=[O:15])[CH3:12])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1
Reactant: CCC[C@H](N)C(=O)OC
Reactant: C[C@H](NC(=O)Cc1ccccc1)C(=O)O
Agent: Cl
Product: CCC[C@H](NC(=O)[C@H](C)NC(=O)Cc1ccccc1)C(=O)OC

Procedure:
Following General Procedure A and using N-(phenylacetyl)-L-alanine (from Example B1 above) and methyl 2-(S)-aminopentanoate hydrochloride (prepared from L-2-aminovaleric acid (Bachem) using General Procedure H (without extractions)), the title compound was prepared as a solid (mp=135-137° C.). The reaction was monitored by tlc (Rf=0.30 in 50% EtOAc/hexanes).
Reaction SMILES: [CH2:1]([Li])CCC.[N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[NH:8][C:7]=1[S:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]([CH2:27][CH3:28])[CH2:24][CH2:23][C:22]2=O.O>[Br-].C[P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O1CCCC1>[N:6]1[C:10]2[CH:11]=[CH:12][CH:13]=[CH:14][C:9]=2[NH:8][C:7]=1[S:15][CH2:16][C:17]1[CH:18]=[CH:19][CH:20]=[C:21]2[C:26]=1[N:25]([CH2:27][CH3:28])[CH2:24][CH2:23][C:22]2=[CH2:1]
Reactant: CCN1CCC(=O)c2cccc(CSc3nc4ccccc4[nH]3)c21
Reactant: [Li]CCCC
Agent: C[P+](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Br-]
Solvent: C1CCOC1
Solvent: O
Product: C=C1CCN(CC)c2c(CSc3nc4ccccc4[nH]3)cccc21
Temperature: -40 °C

Procedure:
To a suspension of methyl triphenylphosphonium bromide (2.65 g)in tetrahydrofuran (50 ml) was added dropwise n-butyllithium (2.2 ml) in a nitrogen flow with stirring at -40° C. After raising the temperature to -20° C., a solution of 8-(2-benzimidazolyl)thiomethyl-1-ethyl-4-oxo-1,2,3,4-tetrahydroquinoline (500 mg) in tetrahydrofuran (5 ml) was added dropwise. The temperature was raised gradually to room temperature, and the mixture was stirred for 3 hours. Water was added to the reaction mixture, and the mixture was extracted with dichloromethane and dried over anhydrous magnesium sulfate. The residue obtained by distilling off the solvent was purified by silica gel column chromatography [eluent:n-hexane-ethyl acetate (3:1)] and recrystallized from diethyl ether-dichloromethane to give 8-(2-benzimidazolyl)thiomethyl-1-ethyl-4-methylene-1,2,3,4-tetrahydroquinoline (390 mg).
Reaction SMILES: [CH2:1]([O:8][C:9]1[C:10]([C:18]([OH:20])=O)=[N:11][NH:12][C:13]=1[C:14]([O:16][CH3:17])=[O:15])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH:27]([OH:31])[CH2:28][NH:29][CH3:30].N1C=CC=C(C(O)CNC)C=1>>[CH2:1]([O:8][C:9]1[C:13]([C:14]([O:16][CH3:17])=[O:15])=[N:12][NH:11][C:10]=1[C:18]([N:29]([CH2:28][CH:27]([OH:31])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=1)[CH3:30])=[O:20])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: COC(=O)c1[nH]nc(C(=O)O)c1OCc1ccccc1
Reactant: CNCC(O)c1ccccn1
Agent: CNCC(O)c1cccnc1
Product: COC(=O)c1n[nH]c(C(=O)N(C)CC(O)c2ccccn2)c1OCc1ccccc1

Procedure:
The title compound was prepared from methyl 4-benzyloxy-3-carboxy-1H-pyrazole-5-carboxylate (prepared as in Example 31, Step 1) using a procedure similar to that described in Example 31, Step 2, except that 1-(2-pyridyl)-2-methylaminoethanol (prepared by the methods of Tsushima, S., et al., EP 278621 and Cudahy, M. M., et al., WO 2003059911) was used in place of 1-(3-pyridyl)-2-methylaminoethanol. ES MS (M+1)=410.
Reaction SMILES: [C:1]1([C:7]2[CH:15]=[C:14]3[C:10]([CH2:11][C:12](=[O:16])[NH:13]3)=[CH:9][CH:8]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH2:17]([N:19]([CH2:35][CH3:36])[CH2:20][CH2:21][CH2:22][NH:23][C:24]([C:26]1[C:30]([CH3:31])=[C:29]([CH:32]=O)[NH:28][C:27]=1[CH3:34])=[O:25])[CH3:18]>>[CH2:35]([N:19]([CH2:17][CH3:18])[CH2:20][CH2:21][CH2:22][NH:23][C:24]([C:26]1[C:30]([CH3:31])=[C:29]([CH:32]=[C:11]2[C:10]3[C:14](=[CH:15][C:7]([C:1]4[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=4)=[CH:8][CH:9]=3)[NH:13][C:12]2=[O:16])[NH:28][C:27]=1[CH3:34])=[O:25])[CH3:36]
Reactant: O=C1Cc2ccc(-c3ccccc3)cc2N1
Reactant: CCN(CC)CCCNC(=O)c1c(C)[nH]c(C=O)c1C
Product: CCN(CC)CCCNC(=O)c1c(C)[nH]c(C=C2C(=O)Nc3cc(-c4ccccc4)ccc32)c1C

Procedure:
6-Phenyl-1,3-dihydroindol-2-one (1.5 g, 7.16 mmol) was condensed with 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylic acid (3-diethylaminopropyl)amide (2 g) to give 1.9 g (57%) of, the title compound as an orange solid.
Reaction SMILES: Cl[C:2]1[C:3]2[NH:10][C:9]([CH3:11])=[C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:4]=2[N:5]=[CH:6][N:7]=1.[CH:17]1([CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3([CH3:33])[O:32][CH2:31][CH2:30][O:29]3)=[CH:24][C:23]=2B2OC(C)(C)C(C)(C)O2)[CH2:19][CH2:18]1>>[CH:17]1([CH2:20][O:21][C:22]2[CH:27]=[CH:26][C:25]([C:28]3([CH3:33])[O:29][CH2:30][CH2:31][O:32]3)=[CH:24][C:23]=2[C:2]2[C:3]3[NH:10][C:9]([CH3:11])=[C:8]([C:12]([O:14][CH2:15][CH3:16])=[O:13])[C:4]=3[N:5]=[CH:6][N:7]=2)[CH2:18][CH2:19]1
Reactant: CC1(c2ccc(OCC3CC3)c(B3OC(C)(C)C(C)(C)O3)c2)OCCO1
Reactant: CCOC(=O)c1c(C)[nH]c2c(Cl)ncnc12
Product: CCOC(=O)c1c(C)[nH]c2c(-c3cc(C4(C)OCCO4)ccc3OCC3CC3)ncnc12

Procedure:
Starting from ethyl 4-chloro-6-methyl-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylate (example A4) and 2-[2-(cyclopropylmethoxy)-5-(2-methyl-1,3-dioxolan-2-yl)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (example B.c13) the title compound is obtained as off-white solid.
Reaction SMILES: [OH:1][N:2]=[C:3]([C:14]#[N:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH3:13])[CH:5]=1.[CH2:16]([S:24](Cl)(=[O:26])=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23].C(N(CC)CC)C>C(#N)C>[CH2:16]([S:24]([O:1][N:2]=[C:3]([C:14]#[N:15])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH3:11])=[C:6]([O:12][CH3:13])[CH:5]=1)(=[O:26])=[O:25])[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH3:23]
Reactant: CCCCCCCCS(=O)(=O)Cl
Reactant: COc1ccc(C(C#N)=NO)cc1OC
Solvent: CCN(CC)CC
Solvent: CC#N
Product: CCCCCCCCS(=O)(=O)ON=C(C#N)c1ccc(OC)c(OC)c1

Procedure:
As described under 1.2, 10.3 g (0.05 mol) of α-hydroxyimino-3,4-dimethoxybenzyl cyanide are reacted with 11.7 g (0.055 mol) of 1-octanesulfonyl chloride in the presence of triethylamine. After recrystallisation of the crude product from ethyl acetate/hexane, 19.1 g (87%) of α-(n-octylsulfonyloxyimino)-3,4-dimethoxybenzyl cyanide are obtained in the form of beige crystals having a melting point of 72-75° C. The 1H-NMR spectrum of the compound shows that it is a pure stereoisomer. The UV spectrum (acetonitrile) of the substance shows a broad absorption band with a maximum at 349 nm (ε=11330) that extends to 435 nm. Elemental analysis: C18H26N2O5S (382.48)
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6](=[O:11])[CH2:5]2.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH2:22]([CH:24]1[C:32]2[C:27](=[N:28][CH:29]=[CH:30][CH:31]=2)[C:26](=O)[O:25]1)[CH3:23].Cl>C1COCC1>[CH2:22]([CH:24]1[C:32]2[C:27](=[N:28][CH:29]=[CH:30][CH:31]=2)[C:26](=[C:5]2[C:4]3[C:8](=[CH:9][CH:10]=[C:2]([F:1])[CH:3]=3)[NH:7][C:6]2=[O:11])[O:25]1)[CH3:23]
Reactant: O=C1Cc2cc(F)ccc2N1
Reactant: CCC1OC(=O)c2ncccc21
Agent: C[Si](C)(C)[N-][Si](C)(C)C
Agent: Cl
Agent: [Li+]
Solvent: C1CCOC1
Product: CCC1OC(=C2C(=O)Nc3ccc(F)cc32)c2ncccc21
Temperature: 0 °C
Reaction time: 0.17 h
Yield: 16.2 %

Procedure:
A solution of 5-fluoro-1,3-dihydro-indol-2-one (966 mg, 6.4 mmol.) in THF (6 mL) is cooled to 0° C. under an Argon atmosphere and treated with a solution of lithium bis(trimethylsilyl)amide (12.8 mL of a 1 M solution in THF, 12.8 mmol) dropwise. The resulting solution is stirred at 0° C. for 10 min and warmed to room temperature. A solution of 5-ethyl-5H-furo[3,4-b]pyridin-7-one, (697 mg, 4.27 mmol) in THF (7 mL) is added dropwise to the reaction mixture. The resulting solution is stirred for 4 h. The reaction mixture is poured into aqueous 10% HCl solution (160 mL). The resulting mixture is heated to 90° C. for 45 min and stirred at room temperature for 36 h. The precipitate which formed is collected by filtration washed with small volumes of ethyl acetate (10×3 mL) and dried to give the title compound as a yellow solid (205 mg, 16%).
Reaction SMILES: Br[C:2]1[CH:3]=[C:4]([N:8]2[C:12]3[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[S:19](=[O:22])(=[O:21])[CH2:20][C:11]=3[C:10]([C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[C:31]1(B(O)O)[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1.[F-].[Cs+]>O1CCOCC1.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>[C:2]1([C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)[CH:7]=[CH:6][CH:5]=[C:4]([N:8]2[C:12]3[C:13]4[CH:14]=[CH:15][CH:16]=[CH:17][C:18]=4[S:19](=[O:22])(=[O:21])[CH2:20][C:11]=3[C:10]([C:23]([N:25]3[CH2:30][CH2:29][O:28][CH2:27][CH2:26]3)=[O:24])=[N:9]2)[CH:3]=1
Reactant: OB(O)c1ccccc1
Reactant: O=C(c1nn(-c2cccc(Br)c2)c2c1CS(=O)(=O)c1ccccc1-2)N1CCOCC1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cs+]
Agent: [F-]
Solvent: O
Solvent: C1COCCO1
Product: O=C(c1nn(-c2cccc(-c3ccccc3)c2)c2c1CS(=O)(=O)c1ccccc1-2)N1CCOCC1
Temperature: 90 °C

Procedure:
1-(3-Bromophenyl)-3-(morpholin-4-ylcarbonyl)-1,4-dihydrothiochromeno[4,3-c]pyrazole 5,5-dioxide (100 mg, 0.20 mmol), phenylboronic acid (37 mg, 0.31 mmol), cesium fluoride (124 mg, 0.82 mmol) are taken in dioxane-water (2:1) and bubbled with nitrogen for 5 min. Then bis(triphenyl phosphine)dichloro palladium(II) (21 g, 0.03 mmol) is added to reaction mass and heated under microwave irradiation for 1 h at 90° C. The reaction mixture is filtered through a celite pad, concentrated under reduced pressure and purified by flash chromatography to afford the title compound as a pale yellow solid. 1H NMR (DMSO-d6, 400 MHz): δ 8.03-8.01 (m,1H), 7.95-7.93 (d, J=8.0 Hz, 1H),7.83 (s, 1H), 7.72-7.70 (m, 4H), 7.68-7.60 (m, 2H), 7.59-7.47 (m, 3H), 7.45-7.40 (m, 1H), 4.91 (s, 2H), 3.96 (m, 4H), 3.62-3.61 (m, 2H). MS (ESI+): 486.0. HPLC (max plot) 98.53%; Rt 4.84 min.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12]([CH3:15])([CH3:14])[CH3:13].[C:16]([Si:18]([CH3:21])([CH3:20])[CH3:19])#[CH:17].N#N>CCN(CC)CC.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.[Cu]I>[C:12]([NH:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:17]#[C:16][Si:18]([CH3:21])([CH3:20])[CH3:19])([CH3:15])([CH3:14])[CH3:13]
Reactant: CC(C)(C)Nc1ccc([N+](=O)[O-])cc1Br
Reactant: C#C[Si](C)(C)C
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Agent: [Cu]I
Agent: N#N
Solvent: CCN(CC)CC
Product: CC(C)(C)Nc1ccc([N+](=O)[O-])cc1C#C[Si](C)(C)C
Temperature: 70 °C
Yield: 15.7 %

Procedure:
To a solution of (2-bromo-4-nitro-phenyl)-tert-butyl-amine (0.6 g, 2.2 mmol) in Et3N (10 mL) was added Pd(PPh3)2Cl2 (70 mg, 0.1 mmol), CuI (20.9 mg, 0.1 mmol) and ethynyl-trimethyl-silane (0.32 g, 3.3 mmol) successively under N2 protection. The reaction mixture was heated at 70° C. overnight. The solvent was removed under vacuum and the residue was washed with EtOAc (10 mL×3). The combined organic layers were washed with water, brine, dried over Na2SO4 and concentrated under vacuum to dryness. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 20:1) to afford tert-butyl-(4-nitro-2-trimethylsilanylethynyl-phenyl)-amine (100 mg, 16%). 1H-NMR (CDCl3, 400 MHz) δ 8.20 (d, J=2.4, Hz, 1H), 8.04 (dd, J=2.4, 9.2 Hz, 1H), 6.79 (d, J=9.6 Hz, 1H), 5.62 (brs, 1H), 1.41 (s, 9H), 0.28 (s, 9H).