Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]([CH2:16][CH2:17][CH2:18][OH:19])[C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(=O)(OC)O[CH2:22][CH:23]=[CH2:24].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CCOCC.CCCCCC>C1COCC1.CCOCC.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]>[CH2:24]([O:19][CH2:18][CH2:17][CH2:16][C@H:9]([NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:10]([O:12][CH:13]([CH3:15])[CH3:14])=[O:11])[CH:23]=[CH2:22]
Reactant: C=CCOC(=O)OC
Reactant: CC(C)OC(=O)[C@H](CCCO)NC(=O)OC(C)(C)C
Agent: [Pd]
Agent: O=C(/C=C/c1ccccc1)/C=C/c1ccccc1
Agent: c1ccc(P(c2ccccc2)c2ccc3ccccc3c2-c2c(P(c3ccccc3)c3ccccc3)ccc3ccccc23)cc1
Solvent: CCOCC
Solvent: C1CCOC1
Solvent: CCCCCC
Product: C=CCOCCC[C@H](NC(=O)OC(C)(C)C)C(=O)OC(C)C
Temperature: 25 °C

Procedure:
A degassed mixture of isopropyl 2(S)-(tert-butoxycarbonylamino)-5-hydroxypentanoate (product of step 26C, 17.6 g, 63.9 mmol), allyl methyl carbonate (24.0 ml, 213 mmol), Pd2(dba)3 (1.62 g, 1.78 mmol) and BINAP (4.42 g, 7.10 mmol) in THF (150 mL) was refluxed under nitrogen for 3 hours. After cooling to room temperature, the reaction was diluted with ether, filtered through celite and evaporated giving a dark brown syrup. Flash chromatography of the residue (silica gel, 30% ether/hexane) gave isopropyl 5-allyloxy-2(S)-(tert-butoxycarbonylamino)pentanoate as a viscous colorless oil, 16.3 g (81%): 1H NMR (300 MHz, Chloroform-D) δ 5.88 (ddt, 1 H, 17.4, 10.4, 5.5), 5.28 (m, 1 H), 5.22-5.11 (m, 1 H), 5.02 (sept., 1 H, J=6.2 Hz), 4.21 (br t, 1 H, J=6.7 Hz), 3.94 (dt, 2 H, J=5.9, 1.5 Hz), 3.42 (t, 2 H, J=5.9 Hz), 1.90-1.82 (m, 1 H), 1.75-1.57 (m, 3 H), 1.42 (s, 9 H), 1.21 (d, 3 H, J=6.2 Hz), 1.19 (d, 3 H, J=6.2 Hz). LCMS m/z 316 (M+H)+.
Reaction SMILES: [OH:1][CH2:2][C:3]([C@H:5]([C@@H:7]([C@@H:9]([CH2:11][OH:12])[OH:10])[OH:8])[OH:6])=[O:4].[O:13]=[CH:14][C@@H:15]([C@H:17]([C@@H:19]([C@@H:21]([CH2:23]O)[OH:22])[OH:20])[OH:18])[OH:16]>O>[CH2:2]([OH:1])[C@H:3]1[O:4][C@H:11]([O:12][CH2:23][C@H:21]2[O:22][C:15]([OH:16])([CH2:14][OH:13])[C@@H:17]([OH:18])[C@@H:19]2[OH:20])[C@H:9]([OH:10])[C@@H:7]([OH:8])[C@@H:5]1[OH:6]
Reactant: O=C(CO)[C@@H](O)[C@H](O)[C@H](O)CO
Reactant: O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
Solvent: O
Product: OC[C@H]1O[C@H](OC[C@H]2OC(O)(CO)[C@@H](O)[C@@H]2O)[C@H](O)[C@@H](O)[C@@H]1O

Procedure:
Specifically, an isomaltooligosaccharide saccharification solution with Bx of 70 to 73 was obtained by adding water to a liquid fructose (HFCS-42, Ingredion Korea) having a fructose content of 42 to 45% (w/w) based on solids and Bx of 75 to 77. To the solution was added a dextrose saccharification enzyme, glucoamylase (AMG, Novozymes Korea), in an amount of 2.0 to 2.5% (w/w) based on the total weight of solids in the saccharification solution at a temperature of 65 to 70° C. and a pH of 4.3 to 4.7, followed by a reaction for 90 to 96 hours. The obtained solution was subject to filtration using diatomite to remove the unreacted materials, decolorization by passing through a column filled with granular active carbon at a temperature of 70 to 75° C., ion purification using a cation exchange resin (PK218, Samyang) and an anion exchange resin (WA30, Samyang), and evaporation to remove moisture to obtain an isomaltulose-containing isomaltooligosaccharide composition with Bx of 75 to 77.
Reaction SMILES: Cl[CH2:2][C:3]#[N:4].[Cl:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][C:12]=1[Cl:13])[NH2:9]>C(Cl)Cl>[Cl:5][C:6]1[CH:7]=[C:8]([CH:10]=[CH:11][C:12]=1[Cl:13])[NH:9][CH2:2][C:3]#[N:4]
Reactant: Nc1ccc(Cl)c(Cl)c1
Reactant: N#CCCl
Solvent: ClCCl
Product: N#CCNc1ccc(Cl)c(Cl)c1
Reaction time: 2 h
Yield: 30 %

Procedure:
Chloroacetonitrile (45.3 grams (g)) and 97.2 g of 3,4-dichloroaniline were heated with stirring in a 250 milliliter (ml) round-bottomed three-necked flask at about 120°-125° C. for 2 hours. The reaction mixture was cooled, then diluted with methylene chloride and then filtered to remove the 3,4-dichloroaniline hydrochloride (52.4 g) which had formed. The filtrate was concentrated to dryness under vacuum, leaving a black gummy residue that crystallized on cooling. The residue was put in solution in hot toluene, the solution was then cooled and filtered, which gave 38.3 g of crude product. Recrystallization from cyclohexane gave 36.2 g of purified 3,4-dichloroanilinoacetonitrile as pink crystals, having a melting point (m.p.) of 95°-97° C.
Reaction SMILES: CS(Cl)(=O)=O.[CH3:6][O:7][C:8]1[CH:19]=[CH:18][CH2:17][C:16]2[C:9]=1[CH:10]=[C:11]1[C:15]=2[CH:14]=[N:13][N:12]1[CH2:20][C@@H:21](O)[CH3:22].C(N(CC)CC)C.[N-:31]=[N+:32]=[N-:33].[Na+].[Cl-].[Na+]>ClCCl.CN(C)C=O>[N:31]([C@H:21]([CH3:22])[CH2:20][N:12]1[C:11]2=[CH:10][C:9]3[C:16]([CH2:17][CH:18]=[CH:19][C:8]=3[O:7][CH3:6])=[C:15]2[CH:14]=[N:13]1)=[N+:32]=[N-:33]
Reactant: [N-]=[N+]=[N-]
Reactant: COC1=C2C=c3c(cnn3C[C@H](C)O)=C2CC=C1
Agent: CS(=O)(=O)Cl
Agent: [Cl-]
Agent: [Na+]
Solvent: ClCCl
Solvent: CN(C)C=O
Solvent: CCN(CC)CC
Product: COC1=C2C=c3c(cnn3C[C@@H](C)N=[N+]=[N-])=C2CC=C1
Yield: 75.5 %

Procedure:
0.4 ml (4.92 mmol) of methanesulfonyl chloride was added dropwise while stirring to a solution, cooled to 0°, of 0.6 g (2.46 mmol) of (S)-1-(7-methoxy-1,4-dihydro-indeno[2,1-c]pyrazol-1-yl)-propan-2-ol and 1.4 ml (9.84 mmol) of triethylamine in 60 ml of dichloromethane and the mixture was stirred at this temperature for a further 1.5 hours. The reaction mixture was subsequently diluted with 100 ml of dichloromethane, washed twice with 50 ml of saturated sodium hydrogen carbonate solution each time and the combined aqueous phases were extracted once with 50 ml of dichloromethane. The combined organic phases were washed with 50 ml of saturated sodium chloride solution, dried over magnesium sulfate and evaporated in a vacuum. The brown oil obtained was dissolved in 40 ml of anhydrous dimethylformamide, treated with 0.32 g (4.92 mmol) of sodium azide and the reaction mixture was heated to 80° for 15 hours while stirring. After cooling, the solution was poured into 80 ml of semi-saturated sodium chloride solution and extracted twice with 80 ml of diethyl ether each time. The combined organic phases were washed once with 80 ml of water and once with 80 ml of saturated sodium chloride solution, dried over magnesium sulfate and the solution was concentrated in a vacuum. The brown oil obtained was purified by column chromatography on silica gel (ethyl acetate/toluene 1:1). 0.5 g (75%) of (R)-1-(2-azido-propyl)-7-methoxy-1,4-dihydro-indeno[2,1-c]pyrazole was obtained as a yellow oil.
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13](=O)[NH:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:22].CCN(C(C)C)C(C)C>ClCCCl>[CH2:1]([S:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([Cl:22])=[N:14][CH:15]=[N:16]2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=P(Cl)(Cl)Cl
Reactant: O=c1[nH]cnc2cc(SCc3ccccc3)ccc12
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCCl
Product: Clc1ncnc2cc(SCc3ccccc3)ccc12
Reaction time: 2 h

Procedure:
A flask was charged with 7-(benzylthio)quinazolin-4(3H)-one (5.0 g, 18.63 mmol) and DCE (93 ml). POCl3 (5.21 ml, 55.9 mmol) was added, followed by Hunig's base (16.27 ml, 93 mmol). The flask was fitted with a reflux condensor, and the reaction was for two hours at 90° C. The reaction was washed with water and the layers were separated. The aqueous layer was extracted with ethyl acetate, and the combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated. The material was purified via column chromatography (RediSep Gold 80 g, gradient elution 0-75% EtOAc:Heptane) to afford 7-(benzylthio)-4-chloroquinazoline as a light yellow solid. (ESI) 287.0 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]([OH:34])([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[CH2:24][CH2:23]2)[C:10](=[O:19])[C:11]#[C:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[N+:35](=[CH2:37])=[N-:36].CN(N=O)S(C1C=CC(C)=CC=1)(=O)=O.[OH-].[K+]>C(OCC)C>[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:20][CH2:21][N:22]2[CH2:23][CH2:24][C:25]([OH:34])([C:28]3[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=3)[CH2:26][CH2:27]2)[C:10]([C:11]2[C:12]([C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=3)=[N:36][NH:35][CH:37]=2)=[O:19])[CH:5]=[CH:6][C:7]=1[Cl:8]
Reactant: C=[N+]=[N-]
Reactant: O=C(C#Cc1ccccc1)C(CCN1CCC(O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1
Agent: Cc1ccc(S(=O)(=O)N(C)N=O)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCOCC
Product: O=C(c1c[nH]nc1-c1ccccc1)C(CCN1CCC(O)(c2ccccc2)CC1)c1ccc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 72 h

Procedure:
A solution of 4-(3,4-dichlorophenyl)-6-(4-hydroxy-4-phenylpiperidino)-1-phenyl-hex-1-yne-3-one (0.30 g) in diethyI ether (25 mL) was cooled to 0° C. and was treated with diazomethane (generated by the reaction of and ethereal solution of N-methyl-N-nitroso-p-toluenesulfonamide with ethanolic potassium hydroxide (Anal. Chem., 45, 2302, 1973)). The resulting mixture was allowed to warm to room temperature and stirred for 3 days. The solvent was evaporated. Radial chromatography, eluting with dichloromethane:methanol (gradient 97.5:2.5, 95:5), afforded the title compound (50 mg) as a white powder; mp 112°-114° C.; NMR: 8.13 (s,1), 7.56-7.26 (m,12), 7.08 (d,1), 4.33 (broad s,1), 2.68 (m,2), 2.37 (m,3), 2.05 (broad s,1), 1.86 (broad s,1), 1.73-1.43 (m,5); MS: m/z=534(M+l). Analysis for C30H29Cl2N3O2 ·0.75 H2O: Calculated: C, 65.75; H, 5.61; N, 7.67; Found: C, 65.71; H, 5.60; N, 7.83.
Reaction SMILES: [F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6](Cl)=[O:7])=[CH:4][CH:3]=1.[C:11]([NH2:19])(=[S:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.N1C=CC=CC=1>CC(C)=O>[F:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([NH:19][C:11](=[S:18])[C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[O:7])=[CH:4][CH:3]=1
Reactant: NC(=S)c1ccccc1
Reactant: O=C(Cl)c1ccc(F)cc1
Solvent: c1ccncc1
Solvent: CC(C)=O
Product: O=C(NC(=S)c1ccccc1)c1ccc(F)cc1
Temperature: 25 °C
Yield: 22.7 %

Procedure:
To a solution of 4-fluorobenzoylchloride (1.3 g, 8.5 mmol) in acetone (7.0 ml) was added a solution of thiobenzamide (1.16 g, 8.5 mmol) and pyridine (0.66 g, 8.5 mmol) in acetone (7.0 ml). The mixture was refluxed for 6 h. and cooled to room temperature. The reaction mixture was poured into water/ice and extracted with chloroform. Flash chromatography on silica gel afforded 0.5 g of the title compound as a red solid.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:10]=[CH:11][C:12]=1[CH2:13][C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([N+:23]([O-])=O)[CH:21]=2)[N:16]([CH3:26])[CH:15]=1)[C:6]([O:8][CH3:9])=[O:7].NC1C=C2C(=CC=1)NC=C2CC1C=CC(C(OC)=O)=CC=1OC>O1CCCC1.[Pd]>[NH2:23][C:20]1[CH:21]=[C:22]2[C:17](=[CH:18][CH:19]=1)[N:16]([CH3:26])[CH:15]=[C:14]2[CH2:13][C:12]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[O:2][CH3:1]
Reactant: COC(=O)c1ccc(Cc2cn(C)c3ccc([N+](=O)[O-])cc23)c(OC)c1
Agent: [Pd]
Agent: COC(=O)c1ccc(Cc2c[nH]c3ccc(N)cc23)c(OC)c1
Solvent: C1CCOC1
Product: COC(=O)c1ccc(Cc2cn(C)c3ccc(N)cc23)c(OC)c1
Yield: 97.5 %

Procedure:
A solution of (E) (0.56 g.) in tetrahydrofuran (30 ml.) was hydrogenated in the presence of palladium-on-carbon (10% w/w; 0.1 g.), as described for the amino ester (A) in Example 1, to give methyl 4-(5-amino-1-methylindol-3-ylmethyl)-3-methoxybenzoate (D) (0.50 g., 98%) as pale yellow foam; NMR: 3.6(s, 3H, NCH3), 3.8(s,3H, CO.OCH3), 3.9(br s,5H, OCH3 and CH2.Ar), 4.45(br,2H, NH2), 6.54(m,2H), 6.86(s,1H), 7.04(m,2H), 7.40(m,2H).
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:6]=[CH:7][C:8]([C:29]#[C:30][Si](C)(C)C)=[C:9]([C:11]([N:13]2[CH2:18][CH2:17][N:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)[CH2:15][CH2:14]2)=[O:12])[CH:10]=1)(=[O:4])=[O:3].C([O-])([O-])=O.[K+].[K+]>CO>[C:29]([C:8]1[CH:7]=[CH:6][C:5]([S:2]([CH3:1])(=[O:4])=[O:3])=[CH:10][C:9]=1[C:11]([N:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=2)[CH2:15][CH2:14]1)=[O:12])#[CH:30]
Reactant: C[Si](C)(C)C#Cc1ccc(S(C)(=O)=O)cc1C(=O)N1CCN(c2ccc(C(F)(F)F)cc2)CC1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: C#Cc1ccc(S(C)(=O)=O)cc1C(=O)N1CCN(c2ccc(C(F)(F)F)cc2)CC1
Temperature: 25 °C
Reaction time: 1 h
Yield: 42 %

Procedure:
To a solution of (5-Methanesulfonyl-2-trimethylsilanylethynyl-phenyl)-[4-(4-trifluoromethyl-phenyl)-piperazin-1-yl]-methanone, Example L (45 mg, 0.0885 mmol) in methanol (0.5 ml) was added K2CO3 (4 mg, 0.0289 mmol). The mixture was stirred at rt for 1 hour. The solvent was removed in vacuo. The residue was purified on SiO2 ,Eluent: Heptane/AcOEt 0%,-40% (10 minutes), then 40% (5 minutes) to provide the title compound (16 mg, 42%, yellow foam), M+H=437.1
Reaction SMILES: [H-].[Na+].[NH:3]1[CH:7]=[CH:6][N:5]=[CH:4]1.[CH3:8][O:9][C:10]1[CH:17]=[CH:16][C:13]([CH2:14]Cl)=[CH:12][CH:11]=1>CN(C)C=O>[NH:3]1[CH:7]=[CH:6][N:5]=[C:4]1[CH2:14][C:13]1[CH:16]=[CH:17][C:10]([O:9][CH3:8])=[CH:11][CH:12]=1
Reactant: COc1ccc(CCl)cc1
Reactant: c1c[nH]cn1
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COc1ccc(Cc2ncc[nH]2)cc1
Reaction time: 0.33 h
Yield: 71.9 %

Procedure:
To a suspension of 5.21 g of 50% sodium hydride in 100 ml of dry dimethylformamide was added slowly 7.39 g of imidazole at room temperature, and the mixture was stirred for 20 minutes. A solution of 20 g of p-methoxybenzyl chloride in 30 ml of dry dimethylformamide was added to the mixture at room temperature over a period of 1 hour, and then the reaction mixture was stirred for 18 hours at 50° C. After removal of the solvent under reduced pressure, 100 ml of dichloromethane was added to the residual oil and the mixture was washed with water and dried over anhydrous magnesium sulfate. The solvent was evaporated and the residual solid was recrystallized from diethyl ether-ligroin to give 14.7 g of p-(1-imidazolylmethyl)anisole as colorless platelets. Then a solution of 14.7 g of p-(1-imidazolylmethyl)anisole in 50 ml of 47% hydrobromic acid was refluxed for 3 hours. After concentration under reduced pressure, the residual solid was recrystallized from ethanol-diethyl ether to give 18.4 g of p-(1-imidazolylmethyl)phenol hydrobromide as colorless platelets. M.P.: 189°-190° C.
Reaction SMILES: CN([CH2:4][C:5]1[C:9]2[CH:10]=[C:11]([Br:14])[CH:12]=[CH:13][C:8]=2[NH:7][CH:6]=1)C.[N+:15]([CH:18]([CH3:20])[CH3:19])([O-:17])=[O:16].[OH-].[Na+]>>[Br:14][C:11]1[CH:10]=[C:9]2[C:8](=[CH:13][CH:12]=1)[NH:7][CH:6]=[C:5]2[CH2:4][C:18]([CH3:20])([N+:15]([O-:17])=[O:16])[CH3:19]
Reactant: CN(C)Cc1c[nH]c2ccc(Br)cc12
Reactant: CC(C)[N+](=O)[O-]
Agent: [Na+]
Agent: [OH-]
Product: CC(C)(Cc1c[nH]c2ccc(Br)cc12)[N+](=O)[O-]

Procedure:
5-Bromogramine, 60.0 g., 165 g. of 2-nitropropane, and 10.5 g. of sodium hydroxide pellets were caused to react under the conditions of Procedure 67C. The product was recovered as a dark syrup-like liquid from which the crystalline product was obtained by dissolving in IPr2O. The crystalline material was recrystallized from IPr2O to yield 48.6 g. of tan crystalline product, m.p. 106°-109°. The structure was confirmed by examination of the NMR spectrum.
Reaction SMILES: [NH:1]1[CH2:6][CH2:5][C:4]2([O:11][C:10]3[C:12]4[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=3[S:8][CH2:7]2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:3][CH2:2]1.Br[CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1>>[CH2:23]([N:1]1[CH2:2][CH2:3][C:4]2([O:11][C:10]3[C:12]4[C:17]([C:18](=[O:21])[C:19](=[O:20])[C:9]=3[S:8][CH2:7]2)=[CH:16][CH:15]=[CH:14][CH:13]=4)[CH2:5][CH2:6]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1
Reactant: O=C1C(=O)c2ccccc2C2=C1SCC1(CCNCC1)O2
Reactant: BrCc1ccccc1
Product: O=C1C(=O)c2ccccc2C2=C1SCC1(CCN(Cc3ccccc3)CC1)O2

Procedure:
Compound 130 was synthesized using spiro[naphtho[1,2-b][1,4]oxathiine-2,4′-piperidine]-5,6-dione, (bromomethyl)benzene and conditions outlined in procedure V. M.p.=170-172° C.; 400 MHz 1H NMR (DMSO-d6) δ: 7.9 (d, 1H), 7.8-7.7 (m, 2H), 7.55 (t, 1H), 7.35-7.2 (m, 5H), 3.55 (s, 2H), 3.05 (s, 2H), 2.7 (d, 2H), 2.35 (t, 2H), 1.95 (d, 2H), 1.8 (t, 2H); LCMS: 392 [M+H].
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH2:8])[CH:3]=1.C(O)C.Cl[CH:13]([CH:19]=O)[C:14]([O:16][CH2:17][CH3:18])=[O:15].C(=O)(O)[O-].[Na+]>C1C=CC=CC=1.C(OCC)(=O)C>[F:1][C:2]1[CH:7]=[CH:6][N:5]2[C:13]([C:14]([O:16][CH2:17][CH3:18])=[O:15])=[CH:19][N:8]=[C:4]2[CH:3]=1
Reactant: CCOC(=O)C(Cl)C=O
Reactant: Nc1cc(F)ccn1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCO
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: CCOC(=O)c1cnc2cc(F)ccn12
Temperature: 60 °C

Procedure:
4-Fluoropyridin-2-amine (10.0 g, 48.0 mmol) was mixed with ethanol (40 mL) in a reaction flask, under an atmosphere of dry nitrogen. A solution of ethyl 2-chloro-3-oxopropanoate (5% in benzene, 178 mL (commercial solution from Toronto Research Chemicals Inc.) was added. The mixture was heated to 60° C. under nitrogen for 4 hours. After allowing the mixture to cool the solvent was removed under vacuum to give a brown solid. The solid was mixed with ethyl acetate (300 mL) and sodium bicarbonate solution (75 mL) and stirred to dissolve. The phases were separated and the bicarbonate solution was extracted further with ethyl acetate (75 mL). The combined ethyl acetate extracts were dried over sodium sulfate, filtered and concentrated under vacuum to give a solid. The crude material was dissolved in ethyl acetate and passed through a short column of silica, eluting with ethyl acetate. Factions containing the desired product were concentrated to give ethyl 7-fluoroimidazo[1,2-a]pyridine-3-carboxylate as a white solid (13 g).
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][N:5]=[C:4]([C:8]([N:10]2[C:18]3[C:13](=[CH:14][C:15]([F:19])=[CH:16][CH:17]=3)[CH2:12][CH2:11]2)=[O:9])[CH:3]=1.[NH:20]1[CH2:25][CH2:24][CH:23]([N:26]2[CH2:31][C:30]3[CH:32]=[CH:33][CH:34]=[N:35][C:29]=3[NH:28][C:27]2=[O:36])[CH2:22][CH2:21]1.CCN(C(C)C)C(C)C>CN(C=O)C>[F:19][C:15]1[CH:14]=[C:13]2[C:18](=[CH:17][CH:16]=1)[N:10]([C:8]([C:4]1[N:5]=[CH:6][N:7]=[C:2]([N:20]3[CH2:21][CH2:22][CH:23]([N:26]4[CH2:31][C:30]5[CH:32]=[CH:33][CH:34]=[N:35][C:29]=5[NH:28][C:27]4=[O:36])[CH2:24][CH2:25]3)[CH:3]=1)=[O:9])[CH2:11][CH2:12]2
Reactant: O=C1Nc2ncccc2CN1C1CCNCC1
Reactant: O=C(c1cc(Cl)ncn1)N1CCc2cc(F)ccc21
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: O=C(c1cc(N2CCC(N3Cc4cccnc4NC3=O)CC2)ncn1)N1CCc2cc(F)ccc21

Procedure:
70 mg (0.25 mmol) (6-chloro-pyrimidin-4-yl)-(5-fluoro-2,3-dihydro-indol-1-yl)-methanone, 60 mg (0.26 mmol) 3-piperidin-4-yl-3,4-dihydro-1H-pyrido[2,3-d]pyrimidin-2-one and 52 μL (0.30 mmol) DIPEA in 5.0 mL DMF were shaken for 2 h at RT. Then the reaction mixture was poured onto water, stirred and the precipitate formed was suction filtered. This was washed with diisopropylether and dried.
Reaction SMILES: [CH2:1]([O:3][C:4]1[N:13]=[C:12]2[C:7]([C:8](=[O:19])[C:9]([C:16]([OH:18])=O)=[CH:10][N:11]2[CH2:14][CH3:15])=[CH:6][CH:5]=1)[CH3:2].[NH2:20][C:21]1[NH:25][N:24]=[N:23][N:22]=1>CN(C)C=O>[CH2:1]([O:3][C:4]1[N:13]=[C:12]2[C:7]([C:8](=[O:19])[C:9]([C:16]([NH:20][C:21]3[NH:25][N:24]=[N:23][N:22]=3)=[O:18])=[CH:10][N:11]2[CH2:14][CH3:15])=[CH:6][CH:5]=1)[CH3:2]
Reactant: CCOc1ccc2c(=O)c(C(=O)O)cn(CC)c2n1
Reactant: Nc1nnn[nH]1
Solvent: CN(C)C=O
Product: CCOc1ccc2c(=O)c(C(=O)Nc3nnn[nH]3)cn(CC)c2n1

Procedure:
7-Ethoxy-1-ethyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (2.0 g) and N,N'-carbonyldiimidazole (1.85 g) in dimethylformamide (40 ml) were stirred and heated to 100° for 7 hours. 5-Amino-1H-tetrazole (1.3 g) was added and the mixture heated at 100° for 1 hour and cooled. The solid was collected and dissolved in hot aqueous dimethylaminoethanol (20 ml, 5%). The hot solution was acidified with hydrochloric acid and the solid was filtered off, washed with water and dried, m.p. above 307° (d), (61%).
Reaction SMILES: Cl[C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]2[CH2:18][C:17]([CH3:20])([CH3:19])[N:16]([O:21][CH:22]3[CH2:27][CH2:26][CH2:25][CH2:24][CH2:23]3)[C:15]([CH3:29])([CH3:28])[CH2:14]2)[N:5]=[C:4]([NH:30][CH2:31][CH2:32][CH2:33][CH2:34][CH:35]2[CH2:40][C:39]([CH3:42])([CH3:41])[N:38]([O:43][CH:44]3[CH2:49][CH2:48][CH2:47][CH2:46][CH2:45]3)[C:37]([CH3:51])([CH3:50])[CH2:36]2)[N:3]=1.[NH2:52][CH2:53][C:54]([OH:56])=[O:55]>>[CH:44]1([O:43][N:38]2[C:37]([CH3:51])([CH3:50])[CH2:36][CH:35]([CH2:34][CH2:33][CH2:32][CH2:31][NH:30][C:4]3[N:5]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][CH2:12][CH:13]4[CH2:14][C:15]([CH3:28])([CH3:29])[N:16]([O:21][CH:22]5[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27]5)[C:17]([CH3:19])([CH3:20])[CH2:18]4)[N:7]=[C:2]([NH:52][CH2:53][C:54]([OH:56])=[O:55])[N:3]=3)[CH2:40][C:39]2([CH3:41])[CH3:42])[CH2:45][CH2:46][CH2:47][CH2:48][CH2:49]1
Reactant: CC1(C)CC(CCCCNc2nc(Cl)nc(NCCCCC3CC(C)(C)N(OC4CCCCC4)C(C)(C)C3)n2)CC(C)(C)N1OC1CCCCC1
Reactant: NCC(=O)O
Product: CC1(C)CC(CCCCNc2nc(NCCCCC3CC(C)(C)N(OC4CCCCC4)C(C)(C)C3)nc(NCC(=O)O)n2)CC(C)(C)N1OC1CCCCC1

Procedure:
The title compound is prepared from the reaction of 2-chloro-4,6-bis[N-(1-cyclohexyloxy-2,2,6,6-tetramethylpiperidin-4-yl)butylamino]-1,3,5-triazine and glycine according to the procedure of Example 15.
Reaction SMILES: [CH2:1]([S:8][C:9]1[N:13]=[C:12]([OH:14])[N:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.F[B-](F)(F)F.[CH3:26][O+](C)C.O>ClCCl>[CH2:1]([S:8][C:9]1[N:13]=[C:12]([O:14][CH3:26])[N:11]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[N:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: Oc1nc(SCc2ccccc2)nn1-c1ccccc1
Reactant: C[O+](C)C
Agent: F[B-](F)(F)F
Solvent: O
Solvent: ClCCl
Product: COc1nc(SCc2ccccc2)nn1-c1ccccc1
Reaction time: 18 h
Yield: 51.5 %

Procedure:
3-Benzylthio-5-hydroxy-1-phenyl-1,2,4-triazole (15 g) in dichloromethane (60 ml) was treated with trimethyloxonium tetrafluoroborate (15.7 g) and allowed to stand for 18 hours at room temperature. The reaction mixture was poured into water (200 ml) and the aqueous layer was washed with dichloromethane (2×100 ml). The dried organic layer was evaporated and then purified by column chromatography (silica/petroleum ether:ether), to give 8.1 g of the desired product.
Reaction SMILES: [F:1][C:2]([F:34])([F:33])[C:3]1[CH:4]=[C:5]([CH:13]=[CH:14][C:15]([NH:17][C@H:18]([C:29]([O:31]C)=[O:30])[CH2:19][C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH:21]=2)=[O:16])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[OH-].[Na+]>CO>[F:11][C:9]([F:10])([F:12])[C:7]1[CH:6]=[C:5]([CH:13]=[CH:14][C:15]([NH:17][C@H:18]([C:29]([OH:31])=[O:30])[CH2:19][C:20]2[C:28]3[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=3)[NH:22][CH:21]=2)=[O:16])[CH:4]=[C:3]([C:2]([F:34])([F:1])[F:33])[CH:8]=1
Reactant: COC(=O)[C@H](Cc1c[nH]c2ccccc12)NC(=O)C=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Product: O=C(C=Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)N[C@@H](Cc1c[nH]c2ccccc12)C(=O)O
Yield: 83.2 %

Procedure:
The same procedures as in Example 64 were carried out from the compound obtained in Example 16 (2.6 g), 1 mol/L of an aqueous sodium hydroxide solution (8.0 mL), and methanol (80 mL), to give the captioned compound (2.1 g, 83%) as crystals.