Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[N:7]=[C:6]2[C:8](I)=[N:9][N:10]([CH3:11])[C:5]2=[CH:4][CH:3]=1.[N:13]1[CH:18]=[CH:17][CH:16]=[C:15](B(O)O)[CH:14]=1>>[Cl:1][C:2]1[N:7]=[C:6]2[C:8]([C:15]3[CH:14]=[N:13][CH:18]=[CH:17][CH:16]=3)=[N:9][N:10]([CH3:11])[C:5]2=[CH:4][CH:3]=1
Reactant: OB(O)c1cccnc1
Reactant: Cn1nc(I)c2nc(Cl)ccc21
Product: Cn1nc(-c2cccnc2)c2nc(Cl)ccc21
Temperature: 70 °C
Reaction time: 2 h

Procedure:
To a solution of 5-chloro-3-iodo-1-methyl-1H-pyrazolo[4,3-b]pyridine (104 mg, 0.354 mmol, containing the isomer 5-chloro-3-iodo-2-methyl-21-1-pyrazolo[4,3-b]pyridine) was added pyridin-3-ylboronic acid (52 mg, 0.425 mmol). The reaction mixture was heated at 70° C. for 1 hr. Then the temperature was raised to 90° C. and the reaction was stirred at 90° C. for 2 h. The reaction was cooled down, washed with sat. NaHCO3, extracted with EtOAc, dried over MgSO4, filtered, concentrated down and purified by silica gel column to give the product. LCMS-ESI+: calc'd for C12H9ClN4: 245.0 (M+H+); Found: 245.3 (M+H+).
Reaction SMILES: [OH:1][C:2]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][C:3]=1[CH:4]=[O:5].C1C(=O)N([Cl:18])C(=O)C1.OS([O-])=O.[Na+]>CC#N>[Cl:18][C:6]1[C:7]([OH:10])=[CH:8][CH:9]=[C:2]([OH:1])[C:3]=1[CH:4]=[O:5]
Reactant: O=C1CCC(=O)N1Cl
Reactant: O=Cc1cc(O)ccc1O
Agent: O=S([O-])O
Agent: [Na+]
Solvent: CC#N
Product: O=Cc1c(O)ccc(O)c1Cl
Temperature: 25 °C
Reaction time: 8 h
Yield: 20.5 %

Procedure:
2,5-dihydroxy-benzaldehyde (100 g, 0.725 mol) was dissolved in MeCN (1L). To the solution was added NCS(N-chlorosuccinimide, 106 g, 1.1 eq) in batches under N2 protection. After addition completed, the mixture was stirred at room temperature overnight. TLC monitored the reaction. After the reaction completed, NaHSO3(38%, 500 mL) was added to the mixture, then extracted with ethyl acetate (3×600 mL) The organic layer was washed with water (2×600 mL) and brine (600 mL), dried over anhydrous MgSO4, concentrated to give a crude product, which was recrystallized to give the desired product 7A (25.6 g, 20.5% yield), as a yellow solid.
Reaction SMILES: [F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C@:9]([OH:24])([C@H:16]([N:18]1[CH2:23][CH2:22][NH:21][CH2:20][CH2:19]1)[CH3:17])[CH2:10][N:11]1[CH:15]=[N:14][CH:13]=[N:12]1.[C:25]1([N:31]=[C:32]=[S:33])[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>>[NH:31]([C:32]([N:21]1[CH2:20][CH2:19][N:18]([C@H:16]([CH3:17])[C@:9]([C:3]2[CH:4]=[CH:5][C:6]([F:8])=[CH:7][C:2]=2[F:1])([OH:24])[CH2:10][N:11]2[CH:15]=[N:14][CH:13]=[N:12]2)[CH2:23][CH2:22]1)=[S:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: S=C=Nc1ccccc1
Reactant: C[C@@H](N1CCNCC1)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Product: C[C@@H](N1CCN(C(=S)Nc2ccccc2)CC1)[C@](O)(Cn1cncn1)c1ccc(F)cc1F
Yield: 80 %

Procedure:
The title compound was prepared similarly to example 8 starting from same piperazine derivative 2 and phenylisothiocyanate. The product was obtained as a colorless solid in 80% yield.
Reaction SMILES: [CH3:1][C:2]1[CH:12]=[CH:11][C:10]([CH3:13])=[C:4]2[C:5]([O:7][C:8](=[O:9])[C:3]=12)=O.Cl.[NH2:15][CH:16]1[CH2:21][CH2:20][C:19](=[O:22])[NH:18][C:17]1=[O:23].C([O-])(=O)C.[Na+]>C(O)(=O)C>[O:23]=[C:17]1[CH:16]([N:15]2[C:5](=[O:7])[C:4]3[C:3](=[C:2]([CH3:1])[CH:12]=[CH:11][C:10]=3[CH3:13])[C:8]2=[O:9])[CH2:21][CH2:20][C:19](=[O:22])[NH:18]1
Reactant: Cc1ccc(C)c2c1C(=O)OC2=O
Reactant: NC1CCC(=O)NC1=O
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Product: Cc1ccc(C)c2c1C(=O)N(C1CCC(=O)NC1=O)C2=O

Procedure:
2-(2,6-Dioxopiperid-3-yl)-4,7-dimethylisoindoline-1,3-dione was prepared by the procedure of Example 1 from 3,6-dimethylphthalic anhydride (220 mg, 1.25 mmol), 3-aminopiperidine-2,6-dione hydrogen chloride (204 mg, 1.24 mmol) and sodium acetate (110 mg, 1.34 mmol) in acetic acid (10 mL). The product is a white solid (200 mg, 56% yield): mp 263.0-265.0° C.; 1H NMR (DMSO-d6) δ2.01-2.07 (m, 1H, CHH), 2.50-2.89 (m, 9H, CH3, CHH, CH2), 5.10 (dd, J=5.1, 12.4 Hz, 1H, NCH), 7.52 (s, 2H, Ar), 11.12 (br s, 1H, NH); 13C NMR (DMSO-d6) δ16.82, 22.02, 30.97, 48.59, 128.01, 135.04, 136.58, 167.68, 169.98, 172.83.
Reaction SMILES: [F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH2:8]([S:10]([N:13]1[CH2:18][CH2:17][CH:16]([C:19]2[C:27]3[C:22](=[C:23]([C:38]([NH2:40])=[O:39])[CH:24]=[C:25]([C:28]4[CH:33]=[C:32]([CH2:34][NH:35][CH3:36])[CH:31]=[C:30]([F:37])[CH:29]=4)[CH:26]=3)[NH:21][CH:20]=2)[CH2:15][CH2:14]1)(=[O:12])=[O:11])[CH3:9].[CH3:41]N>>[F:1][C:2]([F:7])([F:6])[C:3]([OH:5])=[O:4].[CH:36]1([NH:35][CH2:34][C:32]2[CH:33]=[C:28]([C:25]3[CH:26]=[C:27]4[C:22](=[C:23]([C:38]([NH2:40])=[O:39])[CH:24]=3)[NH:21][CH:20]=[C:19]4[CH:16]3[CH2:17][CH2:18][N:13]([S:10]([CH2:8][CH3:9])(=[O:11])=[O:12])[CH2:14][CH2:15]3)[CH:29]=[C:30]([F:37])[CH:31]=2)[CH2:3][CH2:2][CH2:41]1
Reactant: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cc(F)cc(CNC)c4)cc23)CC1
Reactant: CN
Solvent: O=C(O)C(F)(F)F
Product: CCS(=O)(=O)N1CCC(c2c[nH]c3c(C(N)=O)cc(-c4cc(F)cc(CNC5CCC5)c4)cc23)CC1
Yield: 75.2 %

Procedure:
The title compound was prepared according to the general procedure of 3-[1-(ethylsulfonyl)-4-piperidinyl]-5-{3-fluoro-5-[(methylamino)methyl]phenyl}-1H-indole-7-carboxamide trifluoroacetate, substituting cyclobutylamine (21.5 mg, 0.42 mmol) for methanamine to afford 33 mg of the title compound (75.2%).
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]#[N:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[CH:5][CH:4]=1.Cl[C:18]1[C:19]2[CH:26]=[CH:25][NH:24][C:20]=2[N:21]=[CH:22][N:23]=1.C(N(CC)CC)C>C(O)CCC>[Cl:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2([C:15]#[N:16])[CH2:14][CH2:13][N:12]([C:18]3[C:19]4[CH:26]=[CH:25][NH:24][C:20]=4[N:21]=[CH:22][N:23]=3)[CH2:11][CH2:10]2)=[CH:5][CH:4]=1
Reactant: Clc1ncnc2[nH]ccc12
Reactant: N#CC1(c2ccc(Cl)cc2)CCNCC1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CCCCO
Product: N#CC1(c2ccc(Cl)cc2)CCN(c2ncnc3[nH]ccc23)CC1
Yield: 79.7 %

Procedure:
A solution of 4-(4-chlorophenyl)piperidine-4-carbonitrile hydrochloride (0.055 g, 0.2155 mmol), 4-chloro-7H-pyrrolo[2,3-d]pyrimidine (0.033 g, 0.2155 mmol) and triethylamine (0.150 ml, 1.0775 mmol) in n-butanol (2.0 ml) was heated to 100° C. for 2 days. Concentration and trituration with methanol (3 ml) gave a white solid (0.058 g, 80%). LC-MS (LCT2) m/z 338 [M+H+], Rt 6.17 min.
Reaction SMILES: [CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24][NH:25][CH3:26])[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>N1C=CC=CC=1>[CH:1]1([CH2:7][CH2:8][CH2:9][C@@H:10]([C:19]2[O:23][N:22]=[C:21]([CH2:24][N:25]([CH3:26])[S:28]([CH3:27])(=[O:30])=[O:29])[N:20]=2)[CH2:11][C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1
Reactant: CS(=O)(=O)Cl
Reactant: CNCc1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1
Solvent: c1ccncc1
Product: CN(Cc1noc([C@H](CCCC2CCCCC2)CC(=O)OC(C)(C)C)n1)S(C)(=O)=O
Reaction time: 0.33 h
Yield: 75.1 %

Procedure:
A solution of tert-butyl (3R)-6-cyclohexyl-3-{3-[(methylamino)methyl]-1,2,4-oxadiazol-5-yl}hexanoate (preparation 5) (300 mg, 0.82 mmol) in pyridine (2 ml) in a water bath was treated with methanesulphonylchloride (64 μl, 0.82 mmol) and stirred under a nitrogen atmosphere for 20 minutes. The solvent was removed under reduced pressure. The residue was dissolved in EtOAc and washed with 2M HCl followed by brine. The organic extract was dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue was purified on a silica column eluting with a solvent gradient of EtOAc:pentane (5:95) gradually changing to (30:70) to afford the title compound as a colourless oil (273 mg, 75%).
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[CH:5][N:4]=[C:3]1[C:7]#[N:8].Cl.[NH2:10][OH:11].C(N(CC)CC)C>CO>[OH:11][N:10]=[C:7]([C:3]1[N:2]([CH3:1])[CH:6]=[CH:5][N:4]=1)[NH2:8]
Reactant: Cn1ccnc1C#N
Reactant: NO
Agent: Cl
Solvent: CO
Solvent: CCN(CC)CC
Product: Cn1ccnc1C(N)=NO
Temperature: 25 °C
Reaction time: 1 h

Procedure:
1-Methyl-2-cyanoimidazole (0.85 g, 8.0 mmol) (J. Chem. Soc. Perkin Trans. I 1994, 239) was dissolved in methanol (20 mL), then hydroxylamine hydrochloride (0.66 g, 9.6 mmol) and triethylamine (1.3 mL, 9.6 mmol) were added and the mixture was stirred at room temperature for 1 hour. The mixture was chilled in an ice-bath, then the solid was collected by filtration, washed with methanol and dried to give the title compound as a white crystalline solid which was contaminated with triethylamine hydrochloride (0.90 g).
Reaction SMILES: [F:1][C:2]1([F:19])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:18])([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=2)[C:8]([OH:10])=[O:9])[CH2:3]1.O[CH2:21][CH2:22][CH:23]1[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]1>>[F:19][C:2]1([F:1])[CH2:6][CH2:5][C@@H:4]([C@@:7]([OH:18])([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)[C:8]([O:10][CH2:21][CH2:22][CH:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[O:9])[CH2:3]1
Reactant: O=C(O)[C@](O)(c1ccc(Cl)cc1)[C@@H]1CCC(F)(F)C1
Reactant: CC(C)(C)OC(=O)N1CCC(CCO)CC1
Product: O=C(OCCC1CCNCC1)[C@](O)(c1ccc(Cl)cc1)[C@@H]1CCC(F)(F)C1

Procedure:
Using (2R)-2-((1R)-3,3-difluorocyclopentyl)-2-hydroxy-2-(4-chlorophenyl)acetic acid and t-butyl 4-(2-hydroxyethyl)tetrahydro-pyridine-1(2H)-carboxylate, the title compound was prepared by a method similar to steps 2 and 3 of Referential Example 12.
Reaction SMILES: C([O:3][C:4](=O)[CH2:5][C:6]1([OH:21])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH:10]=[CH:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2)C.[NH2:23][NH2:24]>>[OH:21][C:6]1([CH2:5][C:4]([NH:23][NH2:24])=[O:3])[C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[CH:10]=[CH:9][C:8]2[CH:17]=[CH:18][CH:19]=[CH:20][C:7]1=2
Reactant: CCOC(=O)CC1(O)c2ccccc2C=Cc2ccccc21
Reactant: NN
Product: NNC(=O)CC1(O)c2ccccc2C=Cc2ccccc21
Reaction time: 2 h

Procedure:
A mixture of 4.0 g. of 5-hydroxy-dibenzo[a,d]cyclohepten-5-acetic acid ethyl ester and 8 ml. of anhydrous hydrazine is warmed with stirring at temperature of 80°-85° C. for 2 hours, and then allowed to stand at room temperature for 19 hours. The resulting mixture is evaporated to dryness in high vacuum at 100° C., the residue dissolved in hot ethanol, treated with charcoal and crystallized to obtain 5-hydroxy-dibenzo[a,d]cyclohepten-5-acetic acid hydrazide, m.p. 192°-194° C.
Reaction SMILES: [OH:1][C:2]([CH3:24])([CH3:23])[CH2:3][N:4]1[C:12]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:11]2[C:6]([N:7]([CH3:22])[C:8](=[O:21])[N:9]([CH3:20])[C:10]2=[O:19])=[CH:5]1.[Cl:25][C:26]1[O:30][C:29]([CH:31]=O)=[CH:28][CH:27]=1>C1(C)C=CC=CC=1>[Cl:25][C:26]1[O:30][C:29]([CH:31]2[C:5]3=[C:6]4[N:7]([CH3:22])[C:8](=[O:21])[N:9]([CH3:20])[C:10](=[O:19])[C:11]4=[C:12]([C:13]4[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=4)[N:4]3[CH2:3][C:2]([CH3:24])([CH3:23])[O:1]2)=[CH:28][CH:27]=1
Reactant: Cn1c(=O)c2c(-c3ccccc3)n(CC(C)(C)O)cc2n(C)c1=O
Reactant: O=Cc1ccc(Cl)o1
Solvent: Cc1ccccc1
Product: Cn1c(=O)c2c(-c3ccccc3)n3c(c2n(C)c1=O)C(c1ccc(Cl)o1)OC(C)(C)C3

Procedure:
The title compound was prepared from 6-(2-hydroxy-2-methylpropyl)-1,3-dimethyl-5-phenyl-1H-pyrrolo[3,4-d]pyrimidine-2,4(3H,6H)-dione and commercially available 5-chlorofuran-2-carbaldehyde in toluene analogously to Example 12, step 2;
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[CH:3]=1.C(O)(=O)CC.[BH4-].[Na+].[CH3:16][C:17](=O)[CH2:18][CH3:19]>>[CH:17]([NH:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH3:8])[CH:3]=1)([CH2:18][CH3:19])[CH3:16]
Reactant: CCC(C)=O
Reactant: Cc1cccc(N)c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CCC(=O)O
Product: CCC(C)Nc1cccc(C)c1
Temperature: 0 °C

Procedure:
3-Toluidine (107.16 g), 2-butanone (72.11 g) and propionic acid (74.08 g) were stirred and cooled to 0° C. Sodium borohydride (37.83 g) was then added in portions keeping the temperature below 5° C. After allowing to warm to room temperature the reaction mixture was carefully poured onto ice/water. The product was extracted into ethyl acetate, washed with water, 2% hydrochloric acid and finally water again before drying over magnesium sulphate. Evaporation of the solvent under reduced pressure gave a brown oil which was purified by chromatography on silica gel.
Reaction SMILES: C(OC([N:8]1[CH2:17][CH2:16][CH2:15][C:14]2[NH:13][N:12]=[C:11]([C:18]3[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=3)[C:10]=2[CH2:9]1)=O)(C)(C)C.[F:25][C:26]1[CH:27]=[C:28]([CH:31]=[CH:32][C:33]=1[CH3:34])[CH2:29]Br>>[Cl:24][C:21]1[CH:20]=[CH:19][C:18]([C:11]2[C:10]3[CH2:9][NH:8][CH2:17][CH2:16][CH2:15][C:14]=3[N:13]([CH2:29][C:28]3[CH:31]=[CH:32][C:33]([CH3:34])=[C:26]([F:25])[CH:27]=3)[N:12]=2)=[CH:23][CH:22]=1
Reactant: CC(C)(C)OC(=O)N1CCCc2[nH]nc(-c3ccc(Cl)cc3)c2C1
Reactant: Cc1ccc(CBr)cc1F
Product: Cc1ccc(Cn2nc(-c3ccc(Cl)cc3)c3c2CCCNC3)cc1F
Yield: 1.9 %

Procedure:
The title compound (0.002 g) was prepared from 3-(4-chloro-phenyl)-4,6,7,8-tetrahydro-1H-1,2,5-triaza-azulene-5-carboxylic acid tert-butyl ester (Example 59, Step C, 0.1 g) using 3-fluoro-4-methylbenzyl bromide (0.09 g) in place of benzyl chloride in Example 59, Step D. MS (ESI): exact mass calculated for C21H21ClFN3, 369.14; found, m/z 370.1 [M+H]+. 1H NMR (500 MHz, CD3OD): 7.49-7.43 (m, 4H), 7.19 (t, J=7.9 Hz, 1H), 6.88-6.80 (m, 2H), 5.34 (s, 2H), 3.88 (s, 2H), 3.16-3.13 (m, 2H), 2.87-2.85 (m, 2H), 2.23 (d, J=1.5 Hz, 3H), 1.81-1.78 (m, 2H).
Reaction SMILES: [C:1]([CH2:4][C:5](=O)[CH3:6])(=O)[CH3:2].[Cl:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:20]=[N:19][C:18]([NH:21][NH2:22])=[N:17][C:16]=2[CH3:23])=[CH:11][CH:10]=1>CO.C(O)(=O)C>[Cl:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[N:20]=[N:19][C:18]([N:21]3[C:5]([CH3:6])=[CH:4][C:1]([CH3:2])=[N:22]3)=[N:17][C:16]=2[CH3:23])=[CH:13][CH:14]=1
Reactant: CC(=O)CC(C)=O
Reactant: Cc1nc(NN)nnc1-c1ccc(Cl)cc1
Solvent: CC(=O)O
Solvent: CO
Product: Cc1cc(C)n(-c2nnc(-c3ccc(Cl)cc3)c(C)n2)n1
Yield: 85.1 %

Procedure:
A solution of acetylacetone (2.415 g) in methanol (10 ml) was added to a mixture of 6-(4-chlorophenyl)-3-hydrazino-5-methyl-1,2,4-triazine (4.946 g) and acetic acid (3 drops) in methanol (20 ml), and the solution was refluxed for 2 hours with stirring and allowed to stand at room temperature. The resultant crystals were collected by filtration, washed with cold methanol, and dried to give 6-(4-chlorophenyl)-3-(3,5-dimethylpyrazol-1-yl)-5-methyl-1,2,4-triazine (5.354 g), m.p. 151° to 152.5° C.
Reaction SMILES: C([NH:11][CH2:12][C:13]([NH:15][C:16]1[S:17][C:18]([S:21]([NH2:24])(=[O:23])=[O:22])=[N:19][N:20]=1)=[O:14])(OCC1C=CC=CC=1)=O.[BrH:25].C(OCC)C>C(O)(=O)C>[BrH:25].[NH2:11][CH2:12][C:13]([NH:15][C:16]1[S:17][C:18]([S:21]([NH2:24])(=[O:23])=[O:22])=[N:19][N:20]=1)=[O:14]
Reactant: NS(=O)(=O)c1nnc(NC(=O)CNC(=O)OCc2ccccc2)s1
Agent: Br
Solvent: CC(=O)O
Solvent: CCOCC
Product: NCC(=O)Nc1nnc(S(N)(=O)=O)s1
Reaction time: 3 h

Procedure:
The desired compound is prepared by subjecting 2-(N-carbobenzyloxyglycylamino)-1,3,4-thiadiazole-5-sulfonamide (0.5 gram) suspended in glacial acetic acid (5 ml) to a solution of hydrogen bromide in glacial acetic acid (32% w/w, 8.0 ml) at room temperature for 1 hour with stirring. Diethyl ether (50 ml) is then added and the mixture set aside for three hours at 0° C. The solid precipitate is collected, washed with diethyl ether, and dried to give the desired product, 2-(glycylamino)-1,3,4-thiadiazole-5-sulfonamide hydrobromide, m.p. 207°-209° C. (0.4 gram).
Reaction SMILES: [CH2:1]([CH:3]([NH:6][C:7]1[CH:12]=[C:11]([CH3:13])[N:10]=[C:9]([O:14][C:15]2[C:20]([CH3:21])=[CH:19][C:18]([Cl:22])=[CH:17][C:16]=2[CH3:23])[C:8]=1[N+:24]([O-])=O)[CH2:4][CH3:5])[CH3:2]>CC(O)=O.O.[Fe]>[Cl:22][C:18]1[CH:19]=[C:20]([CH3:21])[C:15]([O:14][C:9]2[C:8]([NH2:24])=[C:7]([NH:6][CH:3]([CH2:4][CH3:5])[CH2:1][CH3:2])[CH:12]=[C:11]([CH3:13])[N:10]=2)=[C:16]([CH3:23])[CH:17]=1
Reactant: CCC(CC)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1[N+](=O)[O-]
Agent: [Fe]
Solvent: CC(=O)O
Solvent: O
Product: CCC(CC)Nc1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1N
Temperature: 60 °C

Procedure:
A mixture of (1-ethyl-propyl)-[6-methyl-3-nitro-2-(4-chloro-2,6-dimethyl-phenoxy)-pyridin-yl]-amine (100 mg, 0.265 mmol) and iron (73 mg, 1.33 mmol) in 12 ml of AcOH/H2O (1:1) and heated at 60° C. for 3 hours. The mixture was concentrated to dryness. The residue was diluted with water and extracted with ethyl acetate. The organic layer was dried and concentrated to give the title compound. 1H NMR (CDCl3) δ7.04 (s, 2H), 6.12 (s, 1H), 3.60 (brs, 2H), 3.28 (m, 1H), 2.14 (s, 3H), 2.10 (s, 6H), 1.45-1.80 (m, 4H), 0.97 (t, 6H) ppm.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([C:15]3[N:19]4[CH:20]=[CH:21][C:22]([C:24]([CH3:34])([O:26][Si](CC)(CC)CC)[CH3:25])=[N:23][C:18]4=[N:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]>CCO.Cl>[F:1][C:2]1[CH:3]=[C:4]([C:9]2[N:14]=[C:13]([C:15]3[N:19]4[CH:20]=[CH:21][C:22]([C:24]([OH:26])([CH3:25])[CH3:34])=[N:23][C:18]4=[N:17][CH:16]=3)[CH:12]=[CH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: CC[Si](CC)(CC)OC(C)(C)c1ccn2c(-c3ccnc(-c4ccc(F)c(F)c4)n3)cnc2n1
Agent: Cl
Solvent: CCO
Product: CC(C)(O)c1ccn2c(-c3ccnc(-c4ccc(F)c(F)c4)n3)cnc2n1
Temperature: 25 °C
Reaction time: 12 h
Yield: 33 %

Procedure:
3-[2-(3,4-Difluorophenyl)pyrimidin-4-yl]-7-(1-methyl-1-triethylsilanyloxyethyl)imidazo[1,2-α]pyrimidine in EtOH (8 ml) was treated with conc. HCl (15 drops) and stirred at room temperature for 12 h. The resulting solid was filtered off and dried under reduced pressure. The resulting solid was added to a mixture of 1N NaOH (30 ml) and CH2Cl2 and stirred vigorously for 5 min. The organics were separated and the aqueous fraction extracted with CH2Cl2 (3×20 ml). The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure to yield 2-{3-[2-(3,4-difluorophenyl)pyrimidin-4-yl]imidazo[1,2-α]pyrimidin-7-yl}propan-2-ol (74 mg, 33%): 1H NMR (400 MHz, d6-DMSO) δ 10.16 (1H, d, J 7.3), 8.90 (1H, d, J 5.5), 8.82 (1H, s), 8.40-8.30 (2H, m), 8.03 (1H, d, J 5.5), 7.73 (1H, d, J 7.3), 7.17-7.08 (1H, m), 7.61 (1H, s), 1.55 (6H, s).
Reaction SMILES: Cl[C:2]1[CH:7]=[C:6]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[F:14])[N:5]=[CH:4][N:3]=1.[CH2:15]([OH:19])[CH2:16][C:17]#[CH:18].[H-].[Na+].O>CN(C)C=O>[F:14][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][C:8]=1[C:6]1[CH:7]=[C:2]([O:19][CH2:15][CH2:16][C:17]#[CH:18])[N:3]=[CH:4][N:5]=1
Reactant: Fc1ccccc1-c1cc(Cl)ncn1
Reactant: C#CCCO
Agent: [H-]
Agent: [Na+]
Solvent: O
Solvent: CN(C)C=O
Product: C#CCCOc1cc(-c2ccccc2F)ncn1
Temperature: 25 °C
Reaction time: 12 h
Yield: 57.8 %

Procedure:
In 10 ml of N,N-dimethylformamide were dissolved 450 mg of 4-chloro-6-(2-fluorophenyl)pyrimidine and 227 mg of 3-butyn-1-ol, to which 130 mg of sodium hydride (60% in oil) was added, followed by stirring at room temperature for 12 hours. The reaction mixture was then poured into water and extracted three times with ethyl acetate. The organic layers were combined, washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The resulting residue was subjected to silica gel column chromatography to give 302 mg of 4-(2-fluorophenyl)-6-(3-butynyloxy)pyrimidine (the present compound (152)).
Reaction SMILES: [C:1](#[N:5])[CH2:2][C:3]#[N:4].CC(C)([O-])C.[K+].Br[C:13]([CH3:19])([CH3:18])[C:14]([O:16][CH3:17])=[O:15]>C1COCC1>[C:3]([CH:2]([C:1]#[N:5])[C:13]([CH3:19])([CH3:18])[C:14]([O:16][CH3:17])=[O:15])#[N:4]
Reactant: N#CCC#N
Reactant: COC(=O)C(C)(C)Br
Agent: CC(C)(C)[O-]
Agent: [K+]
Solvent: C1CCOC1
Product: COC(=O)C(C)(C)C(C#N)C#N
Temperature: 50 °C
Reaction time: 0.5 h

Procedure:
A 12 liter 3 neck round bottom flask equipped with a mechanical stirrer, thermometer, condenser and nitrogen bubbler, was charged with malononitrile (251 g, 3.802 moles) and THF (2 liters). Potassium t-butoxide (1M THF, 3.802 L, 3.802 moles) was then added. The mixture was stirred at 50° C. for 30 min. Methyl 2-bromoisobutyrate (688 g, 3.80 moles) was added and the reaction mixture was stirred overnight at 50° C. The reaction was partitioned between aqueous 1N HCl and EtOAc. The organic phase was washed with brine, dried over MgSO4, filtered and concentrated to give the indicated product. 1H NMR (400 MHz, CD3CN): δ 4.35 (s, 1H); 3.73 (s, 3H); 1.43 (s, 6H).
Reaction SMILES: [CH2:1]([Cl:5])[C:2]([OH:4])=[O:3].[C:6]1([CH:12]=[CH:13][C:14]2[CH:15]=[C:16]([OH:24])[C:17]([CH2:21][CH2:22][CH3:23])=[C:18](O)[CH:19]=2)[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1>>[Cl:5][CH2:1][C:2]([O:4][C:18]1[CH:19]=[C:14]([CH:13]=[CH:12][C:6]2[CH:7]=[CH:8][CH:9]=[CH:10][CH:11]=2)[CH:15]=[C:16]([O:24][C:2](=[O:3])[CH2:1][Cl:5])[C:17]=1[CH2:21][CH2:22][CH3:23])=[O:3]
Reactant: O=C(O)CCl
Reactant: CCCc1c(O)cc(C=Cc2ccccc2)cc1O
Product: CCCc1c(OC(=O)CCl)cc(C=Cc2ccccc2)cc1OC(=O)CCl
Yield: 72 %

Procedure:
This material was synthesized from anhydrous chloroacetic and 5-(2-Phenylethenyl)-2-1-propyl-1,3-benzenediol obtained in Example 11 in 72% yield by the same procedure as described in Example 12. 1HNMR (CDCl3, ppm): δ 1.30 (d, J=7.0 Hz, 6H), 3.08 (hept, J=7.0 Hz, 1H), 4.39 (s, 4H), 6.96 (d, J=17 Hz, 1H), 7.14 (d, J=17 Hz, 1H) 7.17 (s, 2H), 7.2-7.5 (m, 5H).
Reaction SMILES: [I:1][C:2]1[CH:7]=[CH:6][C:5]([S:8](Cl)(=[O:10])=[O:9])=[CH:4][CH:3]=1.[NH2:12][C:13]1[S:14][CH:15]=[CH:16][N:17]=1>N1C=CC=CC=1>[I:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:12][C:13]2[S:14][CH:15]=[CH:16][N:17]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1
Reactant: O=S(=O)(Cl)c1ccc(I)cc1
Reactant: Nc1nccs1
Solvent: c1ccncc1
Product: O=S(=O)(Nc1nccs1)c1ccc(I)cc1
Temperature: 25 °C
Reaction time: 72 h
Yield: 53.7 %

Procedure:
4-Iodobenzenesulfonyl chloride (1.8 g, 6.0 mmol, 1.0 equiv) was added portion-wise to a 0° C. solution of 2-aminothiazole (654 mg, 6.53 mmol, 1.1 equiv) in 4.91 mL of anhydrous pyridine. After addition was complete, the reaction mixture was warmed to ambient temperature. After 3 d, the reaction mixture was concentrated in vacuo. The residue was treated with MeOH and ether to precipitate the product. The solid was collected by filtration, washing with ether, to afford the product as a light brown solid (1.18 g, 49%).
Reaction SMILES: Cl[CH2:2][C:3]1[N:8]2[CH:9]=[N:10][N:11]=[C:7]2[C:6]2[S:12][CH:13]=[CH:14][C:5]=2[N:4]=1.CN(C)C=[O:18].[OH-].[Na+]>O1CCOCC1>[N:8]1[CH:9]=[N:10][N:11]2[C:7]=1[C:6]1[S:12][CH:13]=[CH:14][C:5]=1[NH:4][C:3](=[O:18])[CH2:2]2
Reactant: CN(C)C=O
Reactant: ClCc1nc2ccsc2c2nncn12
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Product: O=C1Cn2ncnc2-c2sccc2N1
Temperature: 25 °C
Reaction time: 0.05 h

Procedure:
5. 15.2 g of 5-(chloromethyl)thieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidine are suspended in 650 ml of dioxan and 43 ml of dimethylformamide and cooled to 5° C. 86 ml of 1N sodium hydroxide solution are added thereto within 3 min. and the mixture is stirred at room temperature for 17 h. The reaction mixture is then partitioned between 1.5 l of saturated aqueous sodium chloride solution and 0.7 l of chloroform. The aqueous phase is then made weakly acidic (pH 6) with 12N hydrochloric acid. The mixture is extracted five times with chloroform. The organic extracts are concentrated in a vacuum. The crystalline residue is recrystallized from ethanol. There is obtained 5H-thieno[2,3-f][1,2,4]triazolo[1,5-d][1,4]diazepin-6(7H)-one of m.p. 213°-215° C.
Reaction SMILES: [CH2:1]([N:3]1[C:11]2[N:10]=[CH:9][NH:8][C:7]=2[C:6](=[O:12])[N:5]([CH2:13][CH2:14][CH2:15][CH2:16][P:17](=[O:24])([O:21][CH2:22][CH3:23])[O:18][CH2:19][CH3:20])[C:4]1=[O:25])[CH3:2].Br[CH2:27][CH2:28][CH3:29]>>[CH2:1]([N:3]1[C:11]2[N:10]=[CH:9][N:8]([CH2:27][CH2:28][CH3:29])[C:7]=2[C:6](=[O:12])[N:5]([CH2:13][CH2:14][CH2:15][CH2:16][P:17](=[O:24])([O:18][CH2:19][CH3:20])[O:21][CH2:22][CH3:23])[C:4]1=[O:25])[CH3:2]
Reactant: CCCBr
Reactant: CCOP(=O)(CCCCn1c(=O)c2[nH]cnc2n(CC)c1=O)OCC
Product: CCCn1cnc2c1c(=O)n(CCCCP(=O)(OCC)OCC)c(=O)n2CC

Procedure:
The title substance was prepared from 8.2 mmol of diethyl [4-(3-ethyl-xanthin-1-yl)butyl]phosphonate and 9.8 mmol of bromopropane analogously to Example 30 and chromatographed on silica gel (eluent: dichloromethane/methanol 20:1).