Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [OH:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.[OH-].[K+].[C:13](Cl)(=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22].Cl>O.C(O)(C)C>[C:13]([O:1][C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1)(=[O:23])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH3:22]
Reactant: O=C(O)c1ccc(O)cc1
Reactant: CCCCCCCCCC(=O)Cl
Agent: Cl
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: CCCCCCCCCC(=O)Oc1ccc(C(=O)O)cc1
Temperature: 12.5 °C
Reaction time: 0.25 h

Procedure:
165.7 g (1.2 mol) of para-hydroxybenzoic acid were first dissolved in 400 ml of water and 600 ml of isopropanol and this solution was admixed at 10 to 15° C. with 276.1 g of KOH solution (50% strength by weight aqueous solution, 2.46 mol). The resulting pH was 14. Metered into this solution over the course of two hours, then, at 10 to 15° C., were 228.8 g (1.2 mol) of decanoyl chloride, and the batch was stirred for 15 minutes at 10 to 15° C. thereafter. At the end of the after-stirring, the pH of the reaction mixture was 9.5. The reaction mixture was subsequently admixed at 10 to 15° C. with 30 g of HCl solution (32% strength by weight aqueous solution), and the complete solution was heated to 55 to 60° C. and then adjusted to a pH of 1.5 to 3 using 120 g of HCl solution (32% strength by weight aqueous solution). The reaction mixture was cooled to 20 to 25° C. and the solid was filtered off on a suction filter and washed ten times with 150 ml of water. The yield after drying under reduced pressure at 100° C. was 314.4 g (89.6% of theory). According to HPLC and NMR measurement, the product was free from decanoic acid and from unreacted para-hydroxybenzoic acid. The purity of the product is >99.9% by weight.
Reaction SMILES: [Al+3].[Cl-].[Cl-].[Cl-].[C:5]1([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1.[Br:19][CH2:20][C:21](Br)=[O:22]>ClCCCl>[Br:19][CH2:20][C:21]([C:8]1[CH:9]=[CH:10][C:5]([CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH3:18])=[CH:6][CH:7]=1)=[O:22]
Reactant: O=C(Br)CBr
Reactant: CCCCCCCCc1ccccc1
Agent: [Al+3]
Agent: [Cl-]
Solvent: ClCCCl
Product: CCCCCCCCc1ccc(C(=O)CBr)cc1
Reaction time: 2 h
Yield: 56.8 %

Procedure:
To a flame dried round bottom flask equipped with a magnetic stirbar under an inert atmosphere was added AlCl3 (5.47 g; 41 mmol) followed by 1,2-dichloroethane (22 mL). The stirring suspension was then brought to 0° C. and 1-phenyloctane (7.99 mL, 36 mmol) was added in one portion. Bromoacetyl bromide (3.75 mL, 43 mmol) was then added dropwise over a period of 10 minutes. Upon completing addition of the acid bromide, the reaction mixture was brought to rt and stirred for 2 h. The reaction mixture was then quenched carefully by slow addition of H2O (36 mL) without ever letting the reaction mixture exceed 45° C. producing a suspension of solid white precipitate. The aqueous layer of the quenched reaction mixture was discarded and the organic phase washed once with 10% HCl (10 mL), washed once with H2O (10 mL), and dried over magnesium sulfate. The dried organic phase was then concentrated in vacuo to a green/brown oil. Recrystallization from MeOH/H2O provided the product 1 (6.36 g, 57%) as white needles in three crops. Rf=0.21 (1:19 EtOAc/hexanes).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:11]=3[CH:10]=2)=[CH:5][CH:4]=1.[C:20](Cl)(=[O:27])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.ClCl.[Al+3].[Cl-].[Cl-].[Cl-]>O>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:13][C:12]3[CH:14]=[C:15]([O:18][CH3:19])[CH:16]=[CH:17][C:11]=3[C:10]=2[C:20]([C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:27])=[CH:5][CH:4]=1
Reactant: COc1ccc(-c2cc3ccc(OC)cc3s2)cc1
Reactant: O=C(Cl)c1ccccc1
Agent: ClCl
Agent: [Al+3]
Agent: [Cl-]
Solvent: O
Product: COc1ccc(-c2sc3cc(OC)ccc3c2C(=O)c2ccccc2)cc1
Temperature: 0 °C
Reaction time: 1 h

Procedure:
3 g (11.1 mmol) of 2-(4-methoxyphenyl)-6-methoxybenzo[b]thiophene and 1.55 g (11.1 mmol) of benzoyl chloride were suspended in 150 mL of CH2 Cl2 and cooled to 0° C. The reaction mixture was vigorously stirred and 1.6 g (12 mmol) of AlCl3 was added in several portions over a ten minute time period. The reaction was allowed to proceed for one hour, after which 1 L of water was added to quench the reaction. The organic layer was separated and washed with 100 mL of 1N NaOH, 100 mL of brine, dried by filtration through anhydrous K2CO3, and evaporated to dryness. The crude product was crystallized twice from MeOH. This yielded 1.85 g of the title compound as white crystalline solid.
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[CH:4][N:3]=1.[CH3:11][N:12]([CH3:18])[CH:13]1[CH2:17][CH2:16][NH:15][CH2:14]1>>[CH3:11][N:12]([CH3:18])[CH:13]1[CH2:17][CH2:16][N:15]([C:2]2[N:3]=[CH:4][C:5]([NH2:8])=[CH:6][CH:7]=2)[CH2:14]1
Reactant: CN(C)C1CCNC1
Reactant: O=[N+]([O-])c1ccc(Cl)nc1
Product: CN(C)C1CCN(c2ccc(N)cn2)C1
Yield: 56.3 %

Procedure:
Following General procedure H, 2-chloro-5-nitropyridine (500 mg, 3.1 mmol) was reacted with N,N-dimethylpyrrolidin-3-amine (400 mg, 3.5 mmol) followed by reduction to afford the desired product (360 mg, 56%) as a purple solid: ESI MS m/z 207 [C11H18N4+H]+.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9]1[C:10]([C:14]([OH:16])=O)=[N:11][NH:12][CH:13]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N:17]1([C:23]2[C:24]([CH3:31])=[C:25]([NH2:30])[C:26]([NH2:29])=[CH:27][CH:28]=2)[CH2:22][CH2:21][O:20][CH2:19][CH2:18]1.ON1C2C=CC=CC=2N=N1.CN(C)CCCN=C=NCC>CN(C=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[C:10]([C:14](=[O:16])[NH:30][C:25]2[CH:24]=[CH:31][C:28]([CH2:23][N:17]3[CH2:18][CH2:19][O:20][CH2:21][CH2:22]3)=[CH:27][C:26]=2[NH2:29])=[N:11][NH:12][CH:13]=1)([CH3:2])([CH3:3])[CH3:4]
Reactant: Cc1c(N2CCOCC2)ccc(N)c1N
Reactant: CC(C)(C)OC(=O)Nc1c[nH]nc1C(=O)O
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2ccccc21
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)Nc1c[nH]nc1C(=O)Nc1ccc(CN2CCOCC2)cc1N
Reaction time: 20 h
Yield: 88.6 %

Procedure:
4-tert-Butoxycarbonylamino-1H-pyrazole-3-carboxylic acid (0.750 Kg, 3.30 mol, 1.0 wt), 4-morpholin-4-yl-methyl-benzene-1,2-diamine (0.752 Kg, 3.63 mol, 1.0 wt) and N,N′-dimethylformamide (11.25 L, 15.0 vol) were charged under nitrogen to a flange flask equipped with a mechanical stirrer and thermometer. 1-Hydroxybenzotriazole (HOBT, 0.540 Kg, 3.96 mol, 0.72 wt) was added at 15 to 25° C. N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide (EDC, 0.759 Kg, 3.96 mol, 1.01 wt) was added at 15 to 25° C. and the mixture was stirred at this temperature for 16 to 24 hours. Reaction completion was determined by 1H NMR analysis. The reaction mixture was concentrated under vacuum at 35 to 45° C. The residue was partitioned between ethyl acetate (7.50 L, 10.0 vol) and sat. aq. sodium hydrogen carbonate solution (8.03 L, 10.7 vol) and the layers were separated. The organic phase was washed with brine (3.75 L, 5.0 vol), dried over magnesium sulfate (1.00 Kg, 1.33 wt) and filtered. The filter-cake was washed with ethyl acetate (1.50 L, 2.0 vol). The combined filtrate and wash were concentrated under vacuum at 35 to 45° C. to give [3-(2-amino-4-morpholin-4-ylmethyl-phenylcarbamoyl)-1H-pyrazol-4-yl]-carbamic acid tert-butyl ester (1.217 Kg, 88.6%) as a dark brown solid.
Reaction SMILES: [NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5](Br)=[CH:4][N:3]=1.[F:12][C:13]1[CH:14]=[C:15](B(O)O)[CH:16]=[C:17]([O:19][C:20]2[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=2)[CH:18]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[NH2:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([CH3:10])[C:5]([C:15]2[CH:16]=[C:17]([O:19][C:20]3[CH:25]=[CH:24][C:23]([F:26])=[CH:22][CH:21]=3)[CH:18]=[C:13]([F:12])[CH:14]=2)=[CH:4][N:3]=1
Reactant: OB(O)c1cc(F)cc(Oc2ccc(F)cc2)c1
Reactant: Cc1c(Br)cnc(N)c1C#N
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: Cc1ccccc1
Product: Cc1c(-c2cc(F)cc(Oc3ccc(F)cc3)c2)cnc(N)c1C#N

Procedure:
This compound is prepared in a manner analogous to that of Step D of Example 4, using 1.7 grams (0.008 mole) of 2-amino-5-bromo-3-cyano-4-methylpyridine, 3.0 grams (0.012 mole) of 3-fluoro-5-(4-fluorophenoxy)phenylboronic acid, 4.3 grams (0.031 mole) of potassium carbonate and 0.3 gram of tetrakis(triphenylphosphine)palladium(0) in 150 mL of toluene, yielding 2-amino-3-cyano-4-methyl-5-[3-fluoro-5-(4-fluorophenoxy)phenyl]pyridine.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([NH:8][C:9](=[C:12]([C:15]#[N:16])[C:13]#[N:14])SC)[CH:5]=[CH:6][CH:7]=1.O.[NH2:18][NH2:19]>CCO>[NH2:14][C:13]1[NH:19][N:18]=[C:9]([NH:8][C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=2)[C:12]=1[C:15]#[N:16]
Reactant: CSC(Nc1cccc(Cl)c1)=C(C#N)C#N
Reactant: NN
Solvent: CCO
Solvent: O
Product: N#Cc1c(Nc2cccc(Cl)c2)n[nH]c1N
Temperature: 0 °C

Procedure:
Dissolved 2-(((3-chlorophenyl)amino)(methylthio)methylene)malononitrile in EtOH (100 mL) and added and hydrazine hydrate (1 eq., 2.44 mL), then heated to reflux until complete by TLC (absence of starting material, 18 hrs). Poured into ice water and filtered to obtain 5-amino-3-((3-chlorophenyl)amino)-1H-pyrazole-4-carbonitrile as yellow powder.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[C:11](OC(=O)C)(=[O:13])[CH3:12]>O>[C:11]([O:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6])(=[O:13])[CH3:12]
Reactant: O=C(O)c1cccc(O)c1
Reactant: CC(=O)OC(C)=O
Solvent: O
Product: CC(=O)Oc1cccc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 3 h

Procedure:
3-hydroxybenzoic acid (24.7 grams, 0.2 mole) and acetic anhydride (40.8 grams, 0.4 mole) were mixed and heated to reflux for 3 hours. The reaction mixture was poured into water and stirred for 3 hours at room temperature. The product precipitated, was collected by filtration and recrystallized from chloroform. Yield was 21grams (58%) of white crystals. Melting point was 128°-129.5° C. Proton NMR conducted as in the preceeding preparation, but using (DMSO-d6) gave as peaks, in ppm: 2.24 (s,3H), 7.35, 7.55, 7.65, 7.8 (m, 4H), 13.2 (b, 1H).
Reaction SMILES: [CH3:1][Mg]Br.[CH3:4][C:5]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([Cl:13])[CH:8]=1)=[O:6]>CCOCC>[Cl:13][C:9]1[CH:8]=[C:7]([C:5]([OH:6])([CH3:1])[CH3:4])[CH:12]=[CH:11][CH:10]=1
Reactant: C[Mg]Br
Reactant: CC(=O)c1cccc(Cl)c1
Solvent: CCOCC
Product: CC(C)(O)c1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 18 h
Yield: 93.6 %

Procedure:
Methylmagnesium bromide (3.6 mL, 10.67 mmol, Aldrich, 3 M solution in ether) was added to a cooled (−10° C.) solution of 3-chloroacetophenone (1.5 g, 9.7 mmol) in anhydrous ether slowly over 30 min. After complete addition, the reaction mixture was slowly warmed to room temperature, stirred for 18 hours. Again cooled (−5° C.), than quenched with sat. ammonium chloride solution over 30 min. The reaction mixture was extracted with ether, dried, filtered and concentrated to afford 1.55 g of 2-(3-chlorophenyl)propan-2-ol.
Reaction SMILES: S(S([O-])=O)([O-])=O.[Na+].[Na+].[NH2:9][C:10]1[N:11]=[C:12]([CH2:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)[NH:13][C:14](=[O:24])[C:15]=1[N:16]=NC1C=CC=CC=1>O.CN(C)C=O>[NH2:9][C:10]1[N:11]=[C:12]([CH2:25][C:26]2[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=2)[NH:13][C:14](=[O:24])[C:15]=1[NH2:16]
Reactant: Nc1nc(Cc2ccccc2)[nH]c(=O)c1N=Nc1ccccc1
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: O
Product: Nc1nc(Cc2ccccc2)[nH]c(=O)c1N
Yield: 64.8 %

Procedure:
A solution of sodium dithionite (62 g.) in water (300 ml.) was added dropwise during 30 minutes to a solution of 4-amino-2-benzyl-5-phenylazopyrimid-6-one (27 g.) in dimethylformamide (1000 ml.) at 75° C. The mixture was cooled, and the insoluble solid was filtered off. The filtrate was evaporated in vacuo, the residue was stirred with water, and the solid filtered off. This solid was extracted with boiling water (250 ml.), the extract was filtered hot and then cooled. The solid which separated was recrystallised from water to give 4,5-diamino-2-benzylpyrimid-6-one (12.4 g.) in the form of off-white needles, m.p. 243° C. (with decomposition).
Reaction SMILES: [CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:28]4[CH:33]=[CH:32][CH:31]=[C:30](Br)[CH:29]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2].[CH3:35][N:36]([CH2:38][C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=1B(O)O)[CH3:37]>>[CH2:1]([O:3][C:4]([C:6]1([C:9]2[CH:14]=[CH:13][C:12]([C:15]3[CH:20]=[CH:19][C:18]([C:21]4[O:25][N:24]=[C:23]([CH3:26])[C:22]=4[NH:27][C:28]4[CH:29]=[C:30]([C:40]5[CH:41]=[CH:42][CH:43]=[CH:44][C:39]=5[CH2:38][N:36]([CH3:37])[CH3:35])[CH:31]=[CH:32][CH:33]=4)=[CH:17][CH:16]=3)=[CH:11][CH:10]=2)[CH2:8][CH2:7]1)=[O:5])[CH3:2]
Reactant: CN(C)Cc1ccccc1B(O)O
Reactant: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(Br)c4)cc3)cc2)CC1
Product: CCOC(=O)C1(c2ccc(-c3ccc(-c4onc(C)c4Nc4cccc(-c5ccccc5CN(C)C)c4)cc3)cc2)CC1

Procedure:
Prepared according to the procedure described in Example 42, Step 2, using 1-{4′-[4-(3-bromo-phenylamino)-3-methyl-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid ethyl ester and 2-(N,N-dimethylaminomethyl)-phenylboronic acid.
Reaction SMILES: [NH2:1][C:2]1[N:7]([CH2:8][CH3:9])[C:6](=[O:10])[NH:5][C:4](=[O:11])[C:3]=1[N:12]=O.S(S([O-])=O)([O-])=O.[Na+].[Na+]>>[NH2:12][C:3]1[C:4](=[O:11])[NH:5][C:6](=[O:10])[N:7]([CH2:8][CH3:9])[C:2]=1[NH2:1]
Reactant: CCn1c(N)c(N=O)c(=O)[nH]c1=O
Agent: O=S([O-])S(=O)[O-]
Agent: [Na+]
Product: CCn1c(N)c(N)c(=O)[nH]c1=O

Procedure:
To a suspension of 97 g of 6-amino-1-ethyl-5-nitroso-2,4-(1H,3H)-pyrimidinedione (III) was added 240 g of sodium dithionit in portions. The pale red crystals were filtered off and washed with water. Yield 89 g (99%) IV. NMR (DMSOd6, 2.60), 1.13 (t,3H), 3.30 (s broad, 2H), 3.93 (q,2H), 6.23 (s,2H), 10.00 (s broad, 1H).
Reaction SMILES: [NH:1]1C2(CCCCC2)[NH:4][CH2:3][C:2]1=[O:11].[O:12]1[CH2:22][CH:13]1[CH2:14][C:15]([O:17]CC(C)C)=O>C(#N)C>[CH2:14]1[C:15](=[O:17])[N:4]([CH2:3][C:2]([NH2:1])=[O:11])[CH2:22][CH:13]1[OH:12]
Reactant: O=C1CNC2(CCCCC2)N1
Reactant: CC(C)COC(=O)CC1CO1
Solvent: CC#N
Product: NC(=O)CN1CC(O)CC1=O
Reaction time: 30 h

Procedure:
1 g of 2,2-dimethyl-4-imidazolidinone ((5); R4 =R5 =CH3) (8.76 mmoles) is dissolved in 5 ml acetonitrile. 1 g 2-methylpropyl 3,4-epoxybutanoate ((4); X=isobutyl) (6.32 mmoles) is added and the mixture is boiled for 30 h with stirring. The mixture is cooled, the solvent is decanted off, the resulting dark solid mass is taken up in ethanol, and the solid oxiracetam obtained is filtered off, m.p. 167°-70° C.
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[CH:5]=[C:4]([Cl:16])[CH:3]=1.[C:17](=[O:19])=[O:18]>O1CCCC1.Cl.C(OCC)(=O)C>[Cl:16][C:4]1[CH:3]=[C:2]([CH:7]=[C:6]([O:8][Si:9]([C:12]([CH3:15])([CH3:14])[CH3:13])([CH3:11])[CH3:10])[CH:5]=1)[C:17]([OH:19])=[O:18]
Reactant: CC(C)(C)[Si](C)(C)Oc1cc(Cl)cc(Cl)c1
Reactant: O=C=O
Agent: Cl
Solvent: CCOC(C)=O
Solvent: C1CCOC1
Product: CC(C)(C)[Si](C)(C)Oc1cc(Cl)cc(C(=O)O)c1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 64 %

Procedure:
To “Rieke Mg” (0.21 mol; Rieke, R. D.; Bales, S. E.; Hudnall, P. M.; Burns, T. P.; Poindexter, G. S. Org. Synth. Collective Volume VI, 1988, 845.) in tetrahydrofuran (1000 mL) was added ether 13 (27.7 g, 0.10 mol). After the reaction mixture was stirred for 20 min at ambient temperature there was an exotherm observed. The exotherm subsided within 5 min, and the reaction mixture was cooled to 20° C. with an ice bath. After 15 min, the reaction mixture was cooled to −78° C. To the cool reaction mixture was added CO2 gas for 30 min. The reaction mixture was warmed to ambient temperature, then diluted with cold (0° C.) 10% aqueous HCl (150 mL) and ethyl acetate (400 mL). The aqueous phase was extracted with ethyl acetate (400 mL). The combined organic phases were washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting solid was recrystallized from acetonitrile to provide 14 as fluffy white needles (19.3 g, 64%). 1H NMR (300 MHz, CDCl3) δ 7.70 (s, 1H), 7.43 (s, 1H), 7.08 (s, 1H), 0.99 (s, 9H), 0.23 (s, 6H). IR (KBr) 2957, 1697, 1578, 1434, 1297, 1266, 1115, 990, 871 cm−1.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][C:4]([NH2:7])=[C:3]([NH2:8])[CH:2]=1.[C:9](=S)=[S:10].[Cl-].[Cl-].[Ca+2]>CCO>[NH:7]1[C:4]2[CH:5]=[CH:6][N:1]=[CH:2][C:3]=2[N:8]=[C:9]1[SH:10]
Reactant: S=C=S
Reactant: Nc1ccncc1N
Agent: [Ca+2]
Agent: [Cl-]
Solvent: CCO
Product: Sc1nc2cnccc2[nH]1
Temperature: 25 °C

Procedure:
To a solution of pyridine-3,4-diamine (5 g) in EtOH (80 mL) was added carbon disulfide (10 mL) at room temperature. The mixture was stirred at 40° C. under a dry atmosphere (CaCl2 tube) for 10 h. The mixture was cooled to room temperature. The resulting white solid was collected by filtration and washed with ether to give 1H-imidazo[4,5-c]pyridine-2-thiol (6.1 g) as a white solid.
Reaction SMILES: [Si:1]([O:8][C@@H:9]([C@H:14]1[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[N:15]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[C@@H:10]([CH3:13])[CH2:11]O)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CC(OC(/N=N/C(OC(C)C)=O)=O)C.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(OP(OC2C=CC=CC=2)([N:70]=[N+:71]=[N-:72])=O)=CC=1>C1COCC1>[N:70]([CH2:11][C@H:10]([CH3:13])[C@H:9]([C@H:14]1[CH2:18][O:17][C:16]([CH3:20])([CH3:19])[N:15]1[C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[O:8][Si:1]([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2])=[N+:71]=[N-:72]
Reactant: C[C@@H](CO)[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Reactant: [N-]=[N+]=NP(=O)(Oc1ccccc1)Oc1ccccc1
Agent: CC(C)OC(=O)/N=N/C(=O)OC(C)C
Agent: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Solvent: C1CCOC1
Product: C[C@@H](CN=[N+]=[N-])[C@@H](O[Si](C)(C)C(C)(C)C)[C@H]1COC(C)(C)N1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 8 h
Yield: 84.8 %

Procedure:
To a mixture of tert-butyl (4R)-4-((1R,2S)-1-{[tert-butyl(dimethyl)silyl]oxy}-3-hydroxy-2-methylpropyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate (1.2 g, 3.0 mmol), DIAD (1.2 mL, 5.9 mmol) and PPh3 (1.6 g, 5.9 mmol) in THF (20 mL), diphenylphosphonic azide (1.3 mL, 5.9 mmol) was added. The mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (0-15% EtOAc in hexanes) to provide the sub-title compound (1.09 g, 86%). LCMS calc. for C15H33N4O2Si (M+H-Boc)+: m/z=329.2. found 329.2.
Reaction SMILES: Cl.[NH2:2][N:3]1[CH2:8][C:7]([CH3:9])=[N:6][NH:5][C:4]1=[O:10].[OH-].[Na+].[N:13]1[CH:18]=[CH:17][CH:16]=[C:15]([CH:19]=O)[CH:14]=1>CO.O>[CH3:9][C:7]1[CH2:8][N:3]([N:2]=[CH:19][C:15]2[CH:14]=[N:13][CH:18]=[CH:17][CH:16]=2)[C:4](=[O:10])[NH:5][N:6]=1
Reactant: O=Cc1cccnc1
Reactant: CC1=NNC(=O)N(N)C1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: O
Product: CC1=NNC(=O)N(N=Cc2cccnc2)C1
Temperature: 5 °C
Reaction time: 2 h

Procedure:
To a suspension of 164 g of 4-amino-6-methyl-3-oxo-2,3,4,5-tetrahydro-1,2,4-triazine hydrochloride in 500 ml methanol a 50% NaOH solution is added until a pH of 6 is reached. Now 486 g of a solution containing 22% 3-pyridinaldehyde in water is added maintaining a temperature below 70° C. After the addition is completed the reaction mixture is kept at 65° C. for two hours. Then the suspension is cooled to about 5° C., filtered and dried to yield the title compound.
Reaction SMILES: [CH2:1](Br)[C:2]#[CH:3].[CH2:5]([N:7]1[CH2:12][CH2:11][NH:10][CH2:9][CH2:8]1)[CH3:6].C(=O)([O-])[O-].[Cs+].[Cs+]>CC(C)=O>[CH2:5]([N:7]1[CH2:12][CH2:11][N:10]([CH2:1][C:2]#[CH:3])[CH2:9][CH2:8]1)[CH3:6]
Reactant: CCN1CCNCC1
Reactant: C#CCBr
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: CC(C)=O
Product: C#CCN1CCN(CC)CC1
Temperature: 25 °C
Reaction time: 8 h
Yield: 71.3 %

Procedure:
Propargyl bromide (20.8 g, 175 mmol) was added dropwise to a mixture of 1-ethyl piperazine (20 g, 175 mmol) and cesium carbonate (57 g, 175 mmol) in 350 mL of acetone. The mixture was stirred overnight under nitrogen at room temperature. The inorganic salts were then filtered off, and the solvent was removed. The residue was dissolved in saturated sodium bicarbonate solution and extracted with ethyl acetate. The organic extracts were then evaporated to give 19 g of 1-ethyl-4-prop-2-ynyl-piperazine: mass spectrum (m/e): M+H 153.
Reaction SMILES: [C:1]1([C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=2)=[CH2:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[Br:15]Br>C1CCCCC1>[C:1]1([C:7]([C:9]2[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=2)=[CH:8][Br:15])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=C(c1ccccc1)c1ccccc1
Reactant: BrBr
Solvent: C1CCCCC1
Product: BrC=C(c1ccccc1)c1ccccc1
Reaction time: 20 h
Yield: 83.4 %

Procedure:
20 g (111 mmoles) of 1,1-diphenylethylene was dissolved in 70 ml of cyclohexane, to which was then added dropwise 35 g (222 mmoles) of bromine at room temperature. The mixture was stirred at the same temperature for 20 hours and further heated under reflux for one hour. After cooling, the reaction mixture was washed with a sodium thiosulfate aqueous solution and saturated salt water, and an organic phase was separated by liquid separation. The organic phase was concentrated and subjected to Kugel distillation (at 145 to 148° C./0.6 Torr) to obtain 24 g (yield: 86%) of desired 1,1-diphenyl-2-bromoethylene. 4.8 g (18 mmoles) of 1,1-diphenyl-2-bromoethylene, 0.486 g (20 mmoles) of Mg, a small piece of iodine, and 100 mL of THF were added to a 300 ml eggplant type flask to prepare a Grignard reagent. The reaction mixture was cooled to −78° C., to which trimethoxyborane was then added dropwise while maintaining the same temperature. The mixture was stirred at room temperature for 2 hours, to which 2N hydrochloric acid was then added. An organic phase was treated to isolate desired 1,1-diphenylvinylboronic acid as a white powder in a yield of 35%. The same procedures as in Synthesis Example 4 were followed, except for using 3.28 g of 1,1-diphenylvinylboronic acid in place of the 4-biphenylylboronic acid, to obtain 3.77 g (yield: 72%) of the desired compound.
Reaction SMILES: [CH3:1][C:2]1[S:17][C:5]2[N:6]=[C:7]3[CH:14]=[CH:13][C:12]([C:15]#[N:16])=[CH:11][N:8]3[C:9](=[O:10])[C:4]=2[C:3]=1[CH3:18].[N-:19]=[N+:20]=[N-:21].[Na+].[Cl-].[NH4+].N1C=CC=CC=1>CN(C)C=O>[CH3:1][C:2]1[S:17][C:5]2[N:6]=[C:7]3[CH:14]=[CH:13][C:12]([C:15]4[NH:21][N:20]=[N:19][N:16]=4)=[CH:11][N:8]3[C:9](=[O:10])[C:4]=2[C:3]=1[CH3:18]
Reactant: Cc1sc2nc3ccc(C#N)cn3c(=O)c2c1C
Reactant: [N-]=[N+]=[N-]
Agent: [Cl-]
Agent: [NH4+]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: c1ccncc1
Product: Cc1sc2nc3ccc(-c4nnn[nH]4)cn3c(=O)c2c1C
Yield: 27.6 %

Procedure:
From 0.43 g (0.0017 mol) of 2,3-dimethyl-4-oxo-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidine-7-carbonitrile (Example 32), 0.33 g (0.0051 mol) of sodium azide and 0.3 g (0.0056 mol) of ammonium chloride in 80 ml of dimethylformamide, following the procedure of Example 34, there is obtained 0.14 g of 2,3-dimethyl-7-(1H-tetrazol-5-yl)-4H-pyrido[1,2-a]thieno[2,3-d]pyrimidin-4-one with pyridine (1:0.6); mp 292°-294° C. (dec) after recrystallization from pyridine.