Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([CH3:8])[NH:5][C:4]2=[CH:9][C:10]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:11][C:3]=12.[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>O.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(O)C.C1(C)C=CC=CC=1>[CH3:18][O:19][C:20]1[CH:25]=[CH:24][C:23]([C:2]2[N:7]=[C:6]([CH3:8])[NH:5][C:4]3=[CH:9][C:10]([C:12]4[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=4)=[N:11][C:3]=23)=[CH:22][CH:21]=1
Reactant: COc1ccc(B(O)O)cc1
Reactant: Cc1nc(Cl)c2nc(-c3ccccc3)cc-2[nH]1
Agent: [Pd]
Agent: O=C(C=Cc1ccccc1)C=Cc1ccccc1
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: O
Solvent: Cc1ccccc1
Product: COc1ccc(-c2nc(C)[nH]c3cc(-c4ccccc4)nc2-3)cc1
Temperature: 25 °C
Yield: 86.1 %

Procedure:
A mixture of 4-chloro-2-methyl-6-phenylpyrrolo-[3,2-d]pyrimidine (Example 1(e)) (50 mg, 0.21 mmol), 4-methoxyphenylboronic acid (Aldrich Chemical Company) (44 mg, 0.287 mmol), tris(dibenzylideneacetone) dipalladium(0) (Aldrich Chemical Company) 4.7 mg, 0.0051 mmol, 0.025 eq) and triphenylphosphine (Aldrich Chemical Company) (10.8 mg, 0.041 mmol) in a mixed solvent (600 μL of toluene, 300 μL of 1.0 M Na2CO3, and 150 μL of ethanol) was heated at reflux under N2 for 36 h. upon cooling to the room temperature, the reaction mixture was diluted with H2O (20 mL) and extracted with CHCl3 (3×20 mL). The organic phase was dried over Na2SO4, filtered, and concentrated with a rotary evaporator. The crude material was purified by flash chromatography on silica gel with a gradient eluant of EtOAc(0-50%):hexanes(100-50%) to afford 57 mg (89%) of the title compound as a yellow solid. Mp: 225-227° C. 1H NMR (Acetone-d6, 400 MHz): δ 10.72 (s, 1), 8.14 (d, 2, J=7.0), 8.00 (d, 2, J=8.0), 7.51 (t, 2, J=7.0), 7.44 (t, 1, J=7.0), 7.11 (d, 2, J=8.0), 6.95 (s, 1), 3.91 (s, 3), 2.70 (s, 3). MS m/z: 320 (M+1), 318 (M−1). HRMS (NBA-NaI) m/z Calcd for M++H, C20H17N3O: 316.1450. Found: 316.1450.
Reaction SMILES: [C:1]1([C:11]#[C:12][C:13]2[N:14]=[C:15]([CH:18]3[CH2:23][CH2:22][N:21](C(OC(C)(C)C)=O)[CH2:20][CH2:19]3)[S:16][CH:17]=2)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[CH3:31][C:32]1[N:36]([CH2:37][C:38]([OH:40])=O)[N:35]=[C:34]([C:41]([F:44])([F:43])[F:42])[CH:33]=1>>[CH3:31][C:32]1[N:36]([CH2:37][C:38]([N:21]2[CH2:22][CH2:23][CH:18]([C:15]3[S:16][CH:17]=[C:13]([C:12]#[C:11][C:1]4[C:10]5[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=5)[CH:4]=[CH:3][CH:2]=4)[N:14]=3)[CH2:19][CH2:20]2)=[O:40])[N:35]=[C:34]([C:41]([F:44])([F:43])[F:42])[CH:33]=1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nc(C#Cc3cccc4ccccc34)cs2)CC1
Reactant: Cc1cc(C(F)(F)F)nn1CC(=O)O
Product: Cc1cc(C(F)(F)F)nn1CC(=O)N1CCC(c2nc(C#Cc3cccc4ccccc34)cs2)CC1

Procedure:
tert-Butyl 4-[4-(naphthalen-1-ylethynyl)-1,3-thiazol-2-yl]piperidine-1-carboxylate (IV-6, 200 mg) is deprotected analogously to Example II-2 and then reacted analogously to Example I-81 with [5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetic acid (117 mg). After chromatographic purification, this gives 2-[5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl]-1-{4-[4-(naphthalen-1-ylethynyl)-1,3-thiazol-2-yl]piperidin-1-yl}ethanone (112 mg).
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7](=O)[CH2:8][C:9]([C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][N:12]=1)=[O:10].BrBr.C(N(CC)CC)C.[NH2:27][C:28]([NH2:30])=[S:29].C(=O)([O-])O.[Na+]>C(O)(=O)C>[N:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[C:9]([C:8]1[S:29][C:28]([NH2:30])=[N:27][C:7]=1[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=1)=[O:10]
Reactant: O=C(CC(=O)c1ccccn1)c1ccccn1
Reactant: NC(N)=S
Agent: BrBr
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Product: Nc1nc(-c2ccccn2)c(C(=O)c2ccccn2)s1
Temperature: 80 °C
Reaction time: 1 h
Yield: 50.8 %

Procedure:
1,3-Di(2-pyridyl)propane-1,3-dione (1.17 g, 5.15 mmol) was dissolved in acetic acid (20 mL), and bromine (856 mg, 5.35 mmol) was added thereto, followed by stirring at 80° C. for 1 hour. The reaction mixture was concentrated under reduced pressure, and the resulting residue was suspended in ethanol (30 mL), and triethylamine (0.750 mL, 5.38 mmol) and thiourea (416 mg, 5.47 mmol) were added thereto, followed by stirring under heating and reflux for 30 minutes. Aqueous saturated sodium hydrogencarbonate solution was added to the reaction mixture, followed by extraction with chloroform. The solvent was distilled away under reduced pressure, and the resulting residue was purified through silica gel column chromatography (chloroform:methanol=9:1) to afford the entitled Compound 630 (739 mg, 51%).
Reaction SMILES: NNC(NN=CC1C=CC(Br)=CC=1)=N.[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1.[IH:24].[NH2:25][NH:26][C:27]([NH:29][N:30]=[CH:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=1)=[NH:28]>>[IH:24].[Cl:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=[N:25][NH:26][C:27]([NH:29][N:30]=[CH:31][C:32]2[CH:37]=[CH:36][C:35]([C:38]#[N:39])=[CH:34][CH:33]=2)=[NH:28])=[CH:18][CH:17]=1
Reactant: O=Cc1ccc(Cl)cc1
Reactant: N#Cc1ccc(C=NNC(=N)NN)cc1
Agent: I
Agent: N=C(NN)NN=Cc1ccc(Br)cc1
Product: N#Cc1ccc(C=NNC(=N)NN=Cc2ccc(Cl)cc2)cc1

Procedure:
In a similar manner the reaction of 1-amino-3-(4-bromobenzylideneamino)guanidine methosulfate with 4-chlorobenzaldehyde gives the methosulfate salt of the subject compound. The reaction of 1-amino-3-(4-cyanobenzylideneamino)guanidine hydroiodide with 4-chlorobenzaldehyde gives 1-(4-chlorobenzylideneamino)-3-(4-cyanobenzylideneamino)guanidine hydroiodide; the reaction of 1-amino-3-(4-chlorobenzylideneamino)guanidine hydrochloride with 4-cyanobenzaldehyde affords the corresponding hydrochloride salt which melts at 297°-298°C. The reaction of 1-amino-3-(3,4-dichlorobenzylideneamino)guanidine hydrobromide and 4-chlorobenzaldehyde gives 1-94-chlorobenzylideneamino)-3-(3,4-dichlorobenzylidenamino)guanidine hydrobromide; the reaction of 1-amino-3-(4-chlorobenzylideneamino)guanidine hydrochloride with 3,4-dichlorobenzaldehyde gives the corresponding hydrochloride salt which melts at 288°C.
Reaction SMILES: Cl[C:2]1[C:7]([F:8])=[CH:6][N:5]=[CH:4][C:3]=1[CH:9]=[O:10].[N-:11]=[N+:12]=[N-:13].[Na+]>CN(C=O)C>[N:11]([C:2]1[C:7]([F:8])=[CH:6][N:5]=[CH:4][C:3]=1[CH:9]=[O:10])=[N+:12]=[N-:13]
Reactant: O=Cc1cncc(F)c1Cl
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: [N-]=[N+]=Nc1c(F)cncc1C=O
Temperature: 25 °C
Reaction time: 18 h
Yield: 83.6 %

Procedure:
A mixture of 4-chloro-5-fluoro-pyridine-3-carbaldehyde (4.15 g, 26.0 mmol) and sodium azide (1.86 g, 28.6 mmol) in DMF (15 mL) was stirred at room temperature for 18 hours. The reaction mixture was quenched with brine (200 mL) and extracted with ethyl acetate (3×75 mL). The combined organic extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel flash chromatography (0-50% ethyl acetate in cyclohexane) to afford the title compound as an off-white solid (3.61 g, 84% yield). 1H NMR (300 MHz, CDCl3): δ 10.32 (s, 1H), 8.79 (s, 1H), 8.58 (d, J=3.0 Hz, 1H).
Reaction SMILES: Br[C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][NH:16][C:17](=[O:21])[O:18][CH2:19][CH3:20])[CH2:10][CH2:9]2)=[N:6][CH:7]=1.O[C:23]([C:26](O)(C)C)([CH3:25])[CH3:24].CC(C)=CB([O-])[O-].C(=O)([O-])[O-].[Cs+].[Cs+].O1CCCC1>O>[CH3:25][C:23]([CH3:26])=[CH:24][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:13][CH2:12][CH:11]([CH2:14][CH2:15][NH:16][C:17](=[O:21])[O:18][CH2:19][CH3:20])[CH2:10][CH2:9]2)=[N:6][CH:7]=1
Reactant: CC(C)(O)C(C)(C)O
Reactant: CCOC(=O)NCCC1CCN(c2ccc(Br)cn2)CC1
Agent: CC(C)=CB([O-])[O-]
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: C1CCOC1
Product: CCOC(=O)NCCC1CCN(c2ccc(C=C(C)C)cn2)CC1
Yield: 80.5 %

Procedure:
The process is performed according to the method described in Example 10 (step 10.5.). Starting with 1.00 g (2.81 mmol) of ethyl [2-(5′-bromo-3,4,5,6-tetrahydro-2H-[1,2′]bipyridinyl-4-yl)ethyl]carbamate, prepared in the preceding step, 0.61 g (3.37 mmol) of pinacol 2-methyl-1-propenylboronate (commercial), 2.74 g (8.42 mmol) of caesium carbonate, suspended in 18 mL of a 9/1 mixture of tetrahydrofuran and water, and 0.23 g (0.28 mmol) of PdCl2dppf.CH2Cl2, and after purifying on a column of silica gel, eluting with a 99/1/0.1 mixture of dichloromethane, methanol and 28% aqueous ammonia, 0.75 g of expected product is obtained in the form of a wax.
Reaction SMILES: [CH3:1][O:2][C:3]1[C:8]([C:9]([OH:11])=O)=[CH:7][C:6]([C:12]([NH2:14])=[O:13])=[CH:5][CH:4]=1.[CH3:15][O:16][C:17]1[CH:18]=[C:19]([CH:21]=[C:22]([O:24][CH3:25])[CH:23]=1)[NH2:20]>>[CH3:25][O:24][C:22]1[CH:21]=[C:19]([NH:20][C:9](=[O:11])[C:8]2[CH:7]=[C:6]([CH:5]=[CH:4][C:3]=2[O:2][CH3:1])[C:12]([NH2:14])=[O:13])[CH:18]=[C:17]([O:16][CH3:15])[CH:23]=1
Reactant: COc1ccc(C(N)=O)cc1C(=O)O
Reactant: COc1cc(N)cc(OC)c1
Product: COc1cc(NC(=O)c2cc(C(N)=O)ccc2OC)cc(OC)c1

Procedure:
The captioned compound was synthesized from 6-methoxyisophthalamic acid and 3,5-dimethoxyaniline by the same procedure as in the manufacturing method described in step C of Example 1-3-1.
Reaction SMILES: C(OC([C:6]1[C:7]([CH:13]2[CH2:18][N:17](C(OC(C)(C)C)=O)[CH2:16][CH2:15][N:14]2[C:26]([O:28]C(C)(C)C)=O)=[N:8][C:9]([CH3:12])=[CH:10][CH:11]=1)=O)C.C(O)(C(F)(F)F)=O>ClCCl>[CH3:12][C:9]1[CH:10]=[CH:11][C:6]2[C:26](=[O:28])[N:14]3[CH2:15][CH2:16][NH:17][CH2:18][CH:13]3[C:7]=2[N:8]=1
Reactant: CCOC(=O)c1ccc(C)nc1C1CN(C(=O)OC(C)(C)C)CCN1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: Cc1ccc2c(n1)C1CNCCN1C2=O
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A solution of bis(1,1-dimethylethyl) 2-{3-[(ethyloxy)carbonyl]-6-methyl-2-pyridinyl}-1,4-piperazinedicarboxylate (may be prepared as described in Intermediate 5; 4.96 g) in dichloromethane (200 mL) was cooled to 0° C. and then TFA (20 mL, 260 mmol) was added. This was allowed to warm to room temperature then stirred for 4 hours. The reaction mixture was redissolved in DCM (100 ml), then TFA (10 ml) added and the whole stirred at room temperature for 1.5 hours. The reaction mixture was fully evaporated and azeotroped with toluene. This was dissolved in methanol (200 mL) and then potassium carbonate (3.05 g) was added and the mixture heated to reflux for 8 hours. The methanol was evaporated and then the residue was partitioned between EtOAc and water. The organic layer was then washed with water and then brine, dried through a hydrophobic frit and then evaporated to an orange oil (87 mg), which was found to be impurities.
Reaction SMILES: [C:1](#[N:8])[CH2:2][CH2:3][CH2:4][CH2:5][C:6]#[N:7].[N-:9]=[N+:10]=[N-:11].[Na+].[Cl-].[NH4+]>CN(C=O)C>[NH:7]1[C:6]([CH2:5][CH2:4][CH2:3][CH2:2][C:1]#[N:8])=[N:11][N:10]=[N:9]1
Reactant: N#CCCCCC#N
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: N#CCCCCc1nnn[nH]1
Temperature: 120 °C

Procedure:
A solution of adiponitrile (249 g, 2.3 mol) in DMF (400 mL) was stirred as sodium azide (30 g, 460 mmol) and ammonium chloride (24.7 g, 461 mmol) were added. The reaction was heated at 120° C. for 48 h. The reaction was allowed to cool and concentrated. The residue was dissolved in aqueous ether. The aqueous layer was washed with ether (2×). The combined ether layers were concentrated to afford 1H-tetrazole-5-pentanenitrile as a white solid.
Reaction SMILES: [N:1]1([CH2:6]/[CH:7]=[CH:8]\[C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[S:16]([NH:19][C:20]2[C:29]([C:30]([O:32][CH3:33])=[O:31])=[C:28]3[C:23]([C:24]4[CH:36]=[CH:35][O:34][C:25]=4[CH2:26][O:27]3)=[CH:22][CH:21]=2)(=[O:18])=[O:17])[CH2:5][CH2:4][CH2:3][CH2:2]1.[H][H]>C(O)=O.[OH-].[OH-].[Pd+2]>[N:1]1([CH2:6][CH2:7][CH2:8][C:9]2[CH:14]=[C:13]([F:15])[CH:12]=[CH:11][C:10]=2[S:16]([NH:19][C:20]2[C:29]([C:30]([O:32][CH3:33])=[O:31])=[C:28]3[C:23]([C@H:24]4[CH2:36][CH2:35][O:34][C@H:25]4[CH2:26][O:27]3)=[CH:22][CH:21]=2)(=[O:17])=[O:18])[CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: [H][H]
Reactant: COC(=O)c1c(NS(=O)(=O)c2ccc(F)cc2/C=C\CN2CCCC2)ccc2c1OCc1occc1-2
Agent: [Pd+2]
Agent: [OH-]
Solvent: O=CO
Product: COC(=O)c1c(NS(=O)(=O)c2ccc(F)cc2CCCN2CCCC2)ccc2c1OC[C@@H]1OCC[C@H]21
Reaction time: 1 h
Yield: 98.8 %

Procedure:
A solution of methyl 7-[2-((Z)-3-{pyrrolidin-1-yl}prop-1-enyl)-4-fluorobenzene-sulfonylamino]-4H-furo[2,3-c]chromene-6-carboxylate (Intermediate 15, 0.06 g) in IMS (4 mL) and formic acid (2 drops) was treated under an atmosphere of nitrogen with palladium hydroxide on carbon (10%, 0.02 g). The nitrogen was replaced by hydrogen and the mixture was stirred under an atmosphere of hydrogen for 1 hour. The mixture was filtered through Celite and the filtrate was evaporated to dryness to give methyl cis-(3aRS,9bRS)-7-[2-(3-{pyrrolidin-1-yl}propyl)-4-fluorobenzene-sulfonylamino]-1,3a,4,9b-tetrahydro-2H-furo[2,3-c]chromene-6-carboxylate (0.06 g) which was used without further characterisation.
Reaction SMILES: [NH:1]1[CH:5]=[C:4]([C:6]2[C:7]([C:12]3[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=3)=[N:8][O:9][C:10]=2[CH3:11])[N:3]=[CH:2]1.[C:18]([NH:25][C:26]1[CH:31]=[CH:30][C:29](B(O)O)=[CH:28][CH:27]=1)([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19]>>[C:21]([O:20][C:18](=[O:19])[NH:25][C:26]1[CH:27]=[CH:28][C:29]([N:1]2[CH:5]=[C:4]([C:6]3[C:7]([C:12]4[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=4)=[N:8][O:9][C:10]=3[CH3:11])[N:3]=[CH:2]2)=[CH:30][CH:31]=1)([CH3:24])([CH3:22])[CH3:23]
Reactant: Cc1onc(-c2ccccc2)c1-c1c[nH]cn1
Reactant: CC(C)(C)OC(=O)Nc1ccc(B(O)O)cc1
Product: Cc1onc(-c2ccccc2)c1-c1cn(-c2ccc(NC(=O)OC(C)(C)C)cc2)cn1
Yield: 5 %

Procedure:
As described for Example 3, 4-(1H-imidazol-4-yl)-5-methyl-3-phenyl-isoxazole (112.6 mg, 0.5 mmol) was converted, using 4-(N-Boc-amino)phenylboronic acid instead of 4-fluorophenylboronic acid, to the title compound (10 mg, 5%) which was obtained as a white solid (ESI). MS: m/e=417.0 [M+H]+.
Reaction SMILES: [CH3:1][S:2][CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][CH:10]=[C:9]2[CH:13]([C:18]1[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=1)[CH2:14][CH2:15][C:16]#[N:17].ClC1C=CC=C(C(OO)=[O:36])C=1>ClCCl>[CH3:1][S:2]([CH2:3][C:4]1[CH:5]=[CH:6][CH:7]=[C:8]2[C:12]=1[NH:11][CH:10]=[C:9]2[CH:13]([C:18]1[CH:19]=[CH:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=1)[CH2:14][CH2:15][C:16]#[N:17])=[O:36]
Reactant: CSCc1cccc2c(C(CCC#N)c3ccc(C(F)(F)F)cc3)c[nH]c12
Reactant: O=C(OO)c1cccc(Cl)c1
Solvent: ClCCl
Product: CS(=O)Cc1cccc2c(C(CCC#N)c3ccc(C(F)(F)F)cc3)c[nH]c12
Temperature: 25 °C
Reaction time: 8 h

Procedure:
25 mg (64 μmol) of the compound from Example 35 were introduced into 5 ml of dichloromethane at 0° C., 16 mg (64 μmol) of 70% pure meta-chloroperbenzoic acid were added, and the mixture was stirred at RT overnight. The residue after concentration was purified by preparative HPLC (RP18 column; mobile phase: acetonitrile-water gradient with addition to 0.1% formic acid) to result in 24 mg (92% of theory) of the title compound as mixture of diastereomers.