Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[N:11]1[C:16](=[O:17])[CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[NH:13][C:12]1=[O:22].[C:23](=O)([O-])[O-].[K+].[K+].CI>C(#N)C>[Cl:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N:5][N:6]2[N:11]1[C:16](=[O:17])[CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[N:13]([CH3:23])[C:12]1=[O:22]
Reactant: O=C([O-])[O-]
Reactant: O=c1cc(C(F)(F)F)[nH]c(=O)n1-n1ncc2c(Cl)cccc21
Agent: [K+]
Solvent: CC#N
Solvent: CI
Product: Cn1c(C(F)(F)F)cc(=O)n(-n2ncc3c(Cl)cccc32)c1=O
Temperature: 25 °C
Reaction time: 8 h
Yield: 39.7 %

Procedure:
A mixture of 168B (100 mg, 0.3 mmol), dry acetonitril (3 mL), potassium carbonate (0.05 g, 0.33 mmol) and methyl iodide (0.1 g, 0.7 mmol) is stirred overnight at room temperature. The solids are removed by filtration. The motherliquor is concentrated under reduced pressure. The residue obtained is purified by flash chromatography (ethyl acetate/petrol ether 3/7) which yields the product as an orange semi-solid (41 mg).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[NH:11][C:10](=S)[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1.[OH:20][CH2:21][C:22]([NH:24][NH2:25])=O>C(O)CCC>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[C:22]([CH2:21][OH:20])=[N:24][N:25]=[C:10]3[CH2:9][N:8]=[C:7]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:6]=2[CH:19]=1
Reactant: S=C1CN=C(c2ccccc2)c2cc(Cl)ccc2N1
Reactant: NNC(=O)CO
Solvent: CCCCO
Product: OCc1nnc2n1-c1ccc(Cl)cc1C(c1ccccc1)=NC2

Procedure:
In the manner given in Example 11, a solution of 1,3-dihydro-7chloro-5phenyl-2H-1,4-benzodiazepine-2-thione in n-butyl alcohol was heated to reflux with hydroxyacetic acid hydrazide to give 8-chloro-1-(hydroxymethyl)-6-phenyl-4H-s-triazolo[4,3-a][1,4]benzodiazepine of melting point 204°-206.5° C.
Reaction SMILES: [CH2:1]([O:3][C:4](=[O:41])[C@@H:5]([NH:7][C@H:8]([C:23](=[O:40])[N:24]([C:26]1[N:30](CC2C=CC(OC)=CC=2)[N:29]=[N:28][N:27]=1)[CH3:25])[CH2:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:12][CH:11]=1)[CH3:6])[CH3:2].C(Cl)Cl>C(O)(C(F)(F)F)=O>[CH2:1]([O:3][C:4](=[O:41])[C@@H:5]([NH:7][C@H:8]([C:23](=[O:40])[N:24]([CH3:25])[C:26]1[NH:30][N:29]=[N:28][N:27]=1)[CH2:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([Cl:22])[CH:17]=2)=[CH:14][CH:15]=1)[CH3:6])[CH3:2]
Reactant: CCOC(=O)[C@H](C)N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)N(C)c1nnnn1Cc1ccc(OC)cc1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: CCOC(=O)[C@H](C)N[C@@H](Cc1ccc(-c2cccc(Cl)c2)cc1)C(=O)N(C)c1nnn[nH]1
Yield: 58.2 %

Procedure:
Next, (S)-2-((S)-2-(3′-chloro-biphenyl-4-yl)-1-{[1-(4-methoxy-benzyl)-1H-tetrazol-5-yl]-methyl-carbamoyl}-ethylamino)-propionic acid ethyl ester (260 mg, 0.451 mmol) was dissolved in TFA (5 mL) and DCM (5 mL) and stirred at 50° C. for 12 hours and at 75° C. for 5 hours. The reaction mixture was concentrated under reduced pressure to give (S)-2-{(S)-2-(3′-chloro-biphenyl-4-yl)-1-[methyl-(1H-tetrazol-5-yl)-carbamoyl]-ethylamino}-propionic acid ethyl ester (120 mg). MS: m/z (MW) 457; HPLC retention time 0.95 min (HPLC condition C).
Reaction SMILES: Br[C:2]1[S:3][CH:4]=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[C:9]([C:13]([F:16])([F:15])[F:14])[CH:8]=2)[N:6]=1.[N:17]1([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(=O)([O-])[O-].[K+].[K+].O>CN(C)C=O>[F:14][C:13]([F:16])([F:15])[C:9]1[CH:8]=[C:7]([C:5]2[N:6]=[C:2]([N:20]3[CH2:19][CH2:18][N:17]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22][CH2:21]3)[S:3][CH:4]=2)[CH:12]=[CH:11][CH:10]=1
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Reactant: FC(F)(F)c1cccc(-c2csc(Br)n2)c1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C)OC(=O)N1CCN(c2nc(-c3cccc(C(F)(F)F)c3)cs2)CC1
Yield: 47.9 %

Procedure:
A solution of 2-bromo-4-[3-(trifluoromethyl)phenyl]-1,3-thiazole (2.88 g, 9.35 mmol), tert-butyl piperazine-1-carboxylate (3.48 g, 18.7 mmol) and potassium carbonate (1.29 g, 9.35 mmol) in dimethylformamide (30 ml) was stirred at 120° C. for 12 hours. Water was poured to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with water, and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=9:1) to give 1.85 g (47.9%) of the desired product as an oil.
Reaction SMILES: CCCC[N+](CCCC)(CCCC)CCCC.[F-].[CH3:19][C:20]1[C:21]([NH:32][C:33](=[O:40])[CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[N:22][CH:23]=[C:24]([C:26]#[C:27][Si](C)(C)C)[CH:25]=1>C1COCC1>[C:26]([C:24]1[CH:25]=[C:20]([CH3:19])[C:21]([NH:32][C:33](=[O:40])[CH2:34][N:35]2[CH2:39][CH2:38][CH2:37][CH2:36]2)=[N:22][CH:23]=1)#[CH:27]
Reactant: Cc1cc(C#C[Si](C)(C)C)cnc1NC(=O)CN1CCCC1
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: C#Cc1cnc(NC(=O)CN2CCCC2)c(C)c1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
Under an argon atmosphere 132 mg (0.48 mmol) TBAF are added to a solution of 150 mg (0.48 mmol) N-(3-methyl-5-trimethylsilanylethynyl-pyridin-2-yl)-2-pyrrolidin-1-yl-acetamide in 10 mL THF and the reaction mixture is stirred overnight at RT. The mixture is evaporated down i. vac., the residue is taken up in EtOAc, the organic phase is washed with water and saturated NaCl solution and dried over Na2SO4. After the desiccant and solvent have been eliminated the desired product is obtained.
Reaction SMILES: C(OC([N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH:9]1[C:17]1[CH:22]=[C:21]([Cl:23])[CH:20]=[CH:19][C:18]=1[O:24][CH2:25][C:26]([O:28][CH2:29][CH3:30])=[O:27])=O)(C)(C)C>CCO.Cl.O1CCOCC1>[ClH:23].[CH2:29]([O:28][C:26](=[O:27])[CH2:25][O:24][C:18]1[CH:19]=[CH:20][C:21]([Cl:23])=[CH:22][C:17]=1[CH:9]1[C:10]2[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:16][NH:8]1)[CH3:30]
Reactant: CCOC(=O)COc1ccc(Cl)cc1C1c2ccccc2CN1C(=O)OC(C)(C)C
Agent: Cl
Solvent: C1COCCO1
Solvent: CCO
Product: CCOC(=O)COc1ccc(Cl)cc1C1NCc2ccccc21
Temperature: 25 °C
Reaction time: 18 h

Procedure:
To an ice-cooled solution of (±)-1-(5-chloro-2-ethoxycarbonylmethoxy-phenyl)-1,3-dihydro-isoindole-2-carboxylic acid tert-butyl ester (2.26 g, 5.23 mmol, 1.0 eq.) in EtOH (100 mL), 4M HCl in dioxane (25 mL) was added. The resulting solution was stirred at r.t. for 18 hours. The reaction mixture was concentrated in vacuo. The residue was triturated with cold methyl tert-butyl ether (50 mL), filtered, and rinsed with cold methyl tert-butyl ether (20 mL) to give the desired salt as a white solid.
Reaction SMILES: [OH:1][CH2:2][CH:3]([NH:10][C:11]([C:13]1[NH:14][CH:15]=[C:16]([C:18](=O)[C:19]([CH3:24])=[CH:20]N(C)C)[CH:17]=1)=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH:26]1([NH:29][C:30]([NH2:32])=[NH:31])[CH2:28][CH2:27]1.Cl.C(=O)([O-])[O-].[K+].[K+]>CN(C)C(=O)C.C(OCC)(=O)C>[OH:1][CH2:2][C@@H:3]([NH:10][C:11]([C:13]1[NH:14][CH:15]=[C:16]([C:18]2[C:19]([CH3:24])=[CH:20][N:32]=[C:30]([NH:29][CH:26]3[CH2:28][CH2:27]3)[N:31]=2)[CH:17]=1)=[O:12])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: N=C(N)NC1CC1
Reactant: CC(=CN(C)C)C(=O)c1c[nH]c(C(=O)NC(CO)c2ccccc2)c1
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CC(=O)N(C)C
Product: Cc1cnc(NC2CC2)nc1-c1c[nH]c(C(=O)N[C@H](CO)c2ccccc2)c1
Temperature: 100 °C
Reaction time: 24 h
Yield: 7.1 %

Procedure:
4-(3-Dimethylamino-2-methyl-acryloyl)-1H-pyrrole-2-carboxylic acid (2-hydroxy-1-phenyl-ethyl)-amide (100 mg, 0.29 mmol) was combined with cyclopropyl guanidine•HCl (80 mg) and potassium carbonate (121 mg) in N,N-dimethylacetamide (2 mL). The resulting suspension was heated and stirred at 100° C. for 24 hours. The crude material was diluted with ethyl acetate, washed with saturated NaHCO3 and brine, dried over MgSO4 then concentrated in vacuo. Purification by preparative TLC (silica, 1:1 EtOAc:Hexanes) afforded III-a-162 as a yellow solid (7.8 mg). HPLC Method B, Rt=4.29 minutes; LC/MS(m/z) 378.2 (M+1), 376.2 (M−1); 1H NMR consistent with structure.
Reaction SMILES: [F:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.Cl[C:11]1[C:12]2[C:25]([Cl:26])=[C:24]([CH3:27])[S:23][C:13]=2[N:14]=[C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[N:16]=1>>[N:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:15]1[N:16]=[C:11]([NH:7][CH2:6][C:5]2[CH:8]=[CH:9][C:2]([F:1])=[CH:3][CH:4]=2)[C:12]2[C:25]([Cl:26])=[C:24]([CH3:27])[S:23][C:13]=2[N:14]=1
Reactant: NCc1ccc(F)cc1
Reactant: Cc1sc2nc(-c3ccccn3)nc(Cl)c2c1Cl
Product: Cc1sc2nc(-c3ccccn3)nc(NCc3ccc(F)cc3)c2c1Cl

Procedure:
With the procedure of Example 1, the reaction of 4-fluorobenzylamine with 4-chloro-2-(pyridin-2-yl)-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidine yields 2-(pyridin-2-yl)-4-(4-fluorobenzylamino)-5-chloro-6-methyl-thieno-[2,3-d]-pyrimidine.
Reaction SMILES: [Cl:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([Cl:11])[N:5]=[C:4]([CH3:12])[N:3]=1>C(O)(=O)C.CO.[Fe]>[Cl:1][C:2]1[C:7]([NH2:8])=[C:6]([Cl:11])[N:5]=[C:4]([CH3:12])[N:3]=1
Reactant: Cc1nc(Cl)c([N+](=O)[O-])c(Cl)n1
Agent: [Fe]
Solvent: CC(=O)O
Solvent: CO
Product: Cc1nc(Cl)c(N)c(Cl)n1
Temperature: 65 °C

Procedure:
Add iron powder (6.0 g) to a solution of 4,6 dichloro-2-methyl-5-nitro-pyrimidine (6.50 g, 31 mmol) in acetic acid (11 mL) and MeOH (50 mL). Heat the resulting mixture at 65° C. for 1 h. After cooling, to ambient temperature, filter the mixture through a pad of celite, and evaporate the filtrate to dryness under reduced pressure. Treat the residue with 1N aq NaOH, and extract with EtOAc. Wash the EtOAc extract with water and saturated aq NaCl, dry over Na2SO4, filter, and concentrate in vacuo to obtain the title compound as a solid.
Reaction SMILES: [C:1]1([C:7]2[NH:8][C:9](=[O:18])[O:10][C:11]=2[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[H-].[Na+].[CH2:21](Br)[C:22]#[CH:23].O>CN(C=O)C>[CH2:23]([N:8]1[C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)=[C:11]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][CH:17]=2)[O:10][C:9]1=[O:18])[C:22]#[CH:21]
Reactant: C#CCBr
Reactant: O=c1[nH]c(-c2ccccc2)c(-c2ccccc2)o1
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C#CCn1c(-c2ccccc2)c(-c2ccccc2)oc1=O
Reaction time: 0.33 h
Yield: 45 %

Procedure:
4,5-Diphenyloxazol-2-one (500 mg, 2.11 mmol) was dissolved in DMF (4 ml) and sodium hydride (153 mg, 2.55 mmol) was added under nitrogen and with ice cooling over 20 minutes. After stirring for 20 minutes, propargyl bromide (210 μl, 2.79 mmol) was added. After stirring for 15 minutes with ice cooling and stirring at room temperature for 2 hours, water (20 ml) was added and the mixture was extracted with ethyl acetate. The extract was washed in turn with water and brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography to give 3-(2-propynyl)-4,5-diphenyl-oxazol-2-one.
Reaction SMILES: [Br:1][C:2]1[C:3]([NH:32][CH2:33][C:34]2[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=2)=[C:4]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:28])=[O:27])[CH:5]=[C:6]([CH:8]2[C:17]3[C:16](=[O:18])[CH2:15][CH:14]([CH2:19][CH2:20][CH3:21])[CH2:13][C:12]=3[NH:11][C:10]([CH3:22])=[C:9]2[C:23]#[N:24])[CH:7]=1.[C:42](OC(=O)C)(=[O:44])[CH3:43]>N1C=CC=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:7]=[C:6]([CH:8]2[C:17]3[C:16](=[O:18])[CH2:15][CH:14]([CH2:19][CH2:20][CH3:21])[CH2:13][C:12]=3[NH:11][C:10]([CH3:22])=[C:9]2[C:23]#[N:24])[CH:5]=[C:4]([NH:25][S:26]([CH2:29][CH2:30][CH3:31])(=[O:27])=[O:28])[C:3]=1[N:32]([CH2:33][C:34]1[CH:39]=[CH:38][CH:37]=[C:36]([O:40][CH3:41])[CH:35]=1)[C:42](=[O:44])[CH3:43]
Reactant: CCCC1CC(=O)C2=C(C1)NC(C)=C(C#N)C2c1cc(Br)c(NCc2cccc(OC)c2)c(NS(=O)(=O)CCC)c1
Reactant: CC(=O)OC(C)=O
Solvent: CCOC(C)=O
Solvent: c1ccncc1
Product: CCCC1CC(=O)C2=C(C1)NC(C)=C(C#N)C2c1cc(Br)c(N(Cc2cccc(OC)c2)C(C)=O)c(NS(=O)(=O)CCC)c1
Reaction time: 17 h

Procedure:
A solution of propane-1-sulfonic acid [3-bromo-5-(3-cyano-2-methyl-5-oxo-7-propyl-1,4,5,6,7,8-hexahydro-quinolin-4-yl)-2-(3-methoxy-benzylamino)-phenyl]-amide (120 mg) in pyridine (3 ml) was treated with acetic anhydride (153 μl). After stirring for 17 h, the mixture was diluted with ethyl acetate and washed with water. The organic layer was dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by chromatography on silicagel in heptane/ethyl acetate 1/0→0/1 (v/v) as eluent.