Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.[NH2:2][C:3]1[CH:4]=[C:5]([N:9]2[C:13]([CH3:14])=[C:12]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[CH2:27][CH2:26][CH2:25][CH2:24]4)[CH2:19][CH2:18]3)=[O:16])[C:11]([CH3:28])=[N:10]2)[CH:6]=[CH:7][CH:8]=1.[Cl:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33](Cl)=[O:34]>>[Cl:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][CH:38]=1)[C:33]([NH:2][C:3]1[CH:8]=[CH:7][CH:6]=[C:5]([N:9]2[C:13]([CH3:14])=[C:12]([C:15]([N:17]3[CH2:22][CH2:21][CH:20]([N:23]4[CH2:24][CH2:25][CH2:26][CH2:27]4)[CH2:19][CH2:18]3)=[O:16])[C:11]([CH3:28])=[N:10]2)[CH:4]=1)=[O:34]
Reactant: O=C(Cl)c1cccc(Cl)c1
Reactant: Cc1nn(-c2cccc(N)c2)c(C)c1C(=O)N1CCC(N2CCCC2)CC1
Agent: Cl
Product: Cc1nn(-c2cccc(NC(=O)c3cccc(Cl)c3)c2)c(C)c1C(=O)N1CCC(N2CCCC2)CC1
Yield: 91 %

Procedure:
In analogy to the procedure described in Example 38E], [1-(3-amino-phenyl)-3,5-dimethyl-1H-pyrazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone hydrochloride (Example 38D]) and 3-chlorobenzoyl chloride gave the title compound in 91% yield as light yellow solid. MS: 506.2 (MH+, 1 Cl).
Reaction SMILES: [Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[CH:4]=[C:5]([C:10](=O)[CH3:11])[C:6]([O:8][CH3:9])=[O:7].Cl.[C:19]([NH2:27])(=[NH:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.CC([O-])=O.[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:16]=[C:15]([Cl:17])[CH:14]=[CH:13][C:3]=1[CH:4]1[C:5]([C:6]([O:8][CH3:9])=[O:7])=[C:10]([CH3:11])[NH:27][C:19]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[N:26]1
Reactant: COC(=O)C(=Cc1ccc(Cl)cc1Cl)C(C)=O
Reactant: N=C(N)c1ccccc1
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Na+]
Solvent: CN(C)C=O
Product: COC(=O)C1=C(C)NC(c2ccccc2)=NC1c1ccc(Cl)cc1Cl
Temperature: 60 °C
Yield: 88.8 %

Procedure:
To a stirred solution of methyl 2-(2,4-dichlorobenzylidene)-3-oxobutanoate (480 mg, 1.8 mmol) and benzamidine HCl salt (275 mg, 1.8 mmol) in DMF (6 mL) was added NaOAc (144 mg, 1.8 mmol). The reaction was heated to 60° C. for 3 days and was quenched by 1N HCl (10 mL). The reaction was diluted with EtOAc (10 mL) and the organic layer was washed with 1N HCl, saturated NH4Cl solution (10 mL) and brine (10 mL), dried (MgSO4), filtered and concentrated under reduced pressure to give the crude product as a yellow oil (600 mg). The crude reaction product was moved onto next step without further purification.
Reaction SMILES: [H-].[Na+].[CH2:3]([SH:5])[CH3:4].C(O[CH:10]1[NH:13][C:12](=[O:14])[CH:11]1[CH2:15][CH2:16][CH2:17][NH:18][C:19]([NH:31][C:32]([O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[O:33])=[N:20][C:21]([O:23][CH2:24][C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)=[O:22])(=O)C>C1COCC1>[CH2:3]([S:5][C@@H:10]1[NH:13][C:12](=[O:14])[C@H:11]1[CH2:15][CH2:16][CH2:17][NH:18][C:19]([NH:31][C:32]([O:34][CH2:35][C:36]1[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=1)=[O:33])=[N:20][C:21]([O:23][CH2:24][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][CH:30]=1)=[O:22])[CH3:4]
Reactant: CCS
Reactant: CC(=O)OC1NC(=O)C1CCCNC(=NC(=O)OCc1ccccc1)NC(=O)OCc1ccccc1
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCS[C@@H]1NC(=O)[C@H]1CCCNC(=NC(=O)OCc1ccccc1)NC(=O)OCc1ccccc1
Temperature: -20 °C
Reaction time: 0.5 h
Yield: 37.6 %

Procedure:
To a 0° C. suspension of NaH (60% oil dispersion, 200 mg, 498 mmol) in THF (20 ml) was added ethanethiol (0.37 mL, 4.98 mmol). The resultant mixture was stirred for 10 min, cooled to -20° C., and compound 13 (1.9 g, 3.83 mmol) was added. The solution was stirred further for 30 min at room temperature and concentrated. The residue was partitioned between ethyl acetate and pH 7.0 aqueous buffer. The organic phase was washed with brine, dried (Na ), and concentrated. The residue was purified by silica gel chromatography (EtO2 ) to afford 718 mg (36%) of the title product.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1F.[CH3:12][CH2:13][CH:14]([NH2:17])[CH2:15][OH:16].C(=O)(O)[O-].[Na+]>CN(C=O)C>[F:1][C:2]1[CH:3]=[C:4]([N+:9]([O-:11])=[O:10])[CH:5]=[CH:6][C:7]=1[NH:17][C@H:14]([CH2:13][CH3:12])[CH2:15][OH:16]
Reactant: CCC(N)CO
Reactant: O=[N+]([O-])c1ccc(F)c(F)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC[C@H](CO)Nc1ccc([N+](=O)[O-])cc1F
Temperature: 90 °C
Yield: 98.6 %

Procedure:
This compound was prepared according to General Method 18 (EXAMPLE 45) from 3,4-difluoronitrobenzene (5.34 mL, 0.048 mol), R-(−)-2 amino-1-butanol (4.14 mL, 0.044 mol) and sodium bicarbonate (3.68 g, 0.044 mol) in 133 mL anhydrous DMF heated at 90° C. for 12 hrs to afford 9.9 g (99%) of (2R)-2-(2-fluoro-4-nitrophenyl)amino-1-butanol, a yellow oil, after flash chromatography (gradient elution, hexanes:ethyl acetate 95:5 to 50:50). Data for (2R)-2-(2-fluoro-4-nitrophenyl)amino-1-butanol: 1H NMR (500 MHz, CDCl3) δ 7.98 (dd, J=8.8, 1.5, 1H), 7.89 (dd, J=11.7, 2.4, 1H), 6.71 (dd, J=8.8, 8.8, 1H), 4.72 (bs, 1H), 3.81 (m, 1H), 3.73 (m, 1H), 3.55 (m, 1H), 1.76 (m, 1H), 1.63 (m, 1H), 1.02 (t, J=7.8, 3H).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([OH:26])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH3:25])[N:9]=2)[CH:7]=1.I[CH2:28][CH3:29].C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:26][CH2:28][CH3:29])=[C:6]([C:8]2[C:12]([NH:13][C:14]([C:16]3[CH:17]=[N:18][N:19]4[CH:24]=[CH:23][CH:22]=[N:21][C:20]=34)=[O:15])=[CH:11][N:10]([CH3:25])[N:9]=2)[CH:7]=1
Reactant: Cn1cc(NC(=O)c2cnn3cccnc23)c(-c2cc(Cl)ccc2O)n1
Reactant: CCI
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCOc1ccc(Cl)cc1-c1nn(C)cc1NC(=O)c1cnn2cccnc12
Temperature: 45 °C
Reaction time: 3 h
Yield: 52.8 %

Procedure:
To a solution of N-(3-(5-chloro-2-hydroxyphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide (61.1 mg, 0.166 mmol) in 3.0 mL acetone was added iodoethane (26.0 μL, 0.325 mmol) and potassium carbonate (70.6 mg, 0.511 mmol) The reaction was stirred at 45° C. for 3 hours. The reaction mixture was partitioned between ethyl acetate and water, and the organic portion washed with brine, dried over magnesium sulfate, and concentrated. The crude product was purified by reverse phase HPLC and lyophilized to give 34.8 mg (54%) N-(3-(5-chloro-2-ethoxyphenyl)-1-methyl-1H-pyrazol-4-yl)pyrazolo[1,5-a]pyrimidine-3-carboxamide. LCMS (ESI) m+H=397.1; 1H NMR (400 MHz, DMSO-d6) δ: 9.68 (s, 1H), 9.33 (dd, J=7.0, 1.6, 1H), 8.73 (dd, J=4.2, 1.6, 1H), 8.66 (s, 1H), 8.28 (s, 1H), 7.46 (dd, J=8.8, 2.7, 1H), 7.38 (d, J=2.7, 1H), 7.32-7.23 (m, 2H), 4.12 (q, J=6.9, 2H), 3.91 (s, 3H), 1.04 (t, J=6.9, 3H).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[CH:15]=1)[NH:5][CH2:6][CH2:7][N:8]1[CH2:12][CH2:11][CH2:10][CH2:9]1.Cl[C:26]1[CH:27]=[CH:28][C:29]2[N:30]=[CH:31][N:32]=[C:33]([NH2:36])[C:34]=2[N:35]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.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>[F:1][C:2]1[CH:15]=[C:14]([C:26]2[CH:27]=[CH:28][C:29]3[N:30]=[CH:31][N:32]=[C:33]([NH2:36])[C:34]=3[N:35]=2)[CH:13]=[C:4]([NH:5][CH2:6][CH2:7][N:8]2[CH2:9][CH2:10][CH2:11][CH2:12]2)[CH:3]=1
Reactant: Nc1ncnc2ccc(Cl)nc12
Reactant: CC1(C)OB(c2cc(F)cc(NCCN3CCCC3)c2)OC1(C)C
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: [Cs+]
Solvent: C1COCCO1
Solvent: O
Product: Nc1ncnc2ccc(-c3cc(F)cc(NCCN4CCCC4)c3)nc12
Temperature: 90 °C
Reaction time: 2 h

Procedure:
A suspension of crude 31-B (300 mg, 1.0 mmol), 3-A (150 mg, 0.80 mmol), Pd(PPh3)4 (30 mg) and Cs2CO3 (600 mg, 1.8 mmol) in dioxane/H2O (10 mL/1.0 mL) was stirred at 90° C. for 2 h. The reaction solution was partitioned between EtOAc (100 mL) and brine (35 mL). The combined organic layer was washed with water (3×30 mL), concentrated and purified by prep-HPLC (25 mg, 8.9%). LCMS (0-60AB), RT=0.904 min, M+H 352.9 1H-NMR (Methanol-d4, 400 MHz): δ 8.53 (s, 1H), 8.35 (s, 1H), 8.23 (d, J=8.8 Hz, 1H), 8.03 (d, J=8.8 Hz, 1H)), 7.33 (s, 1H), 7.24 (d, J=10.4 Hz, 1H), 6.49 (d, J=11.2 Hz, 1H), 3.60-3.57 (m, 2H), 3.37-3.28 (m, 6H), 2.07-2.04 (m, 2H).
Reaction SMILES: [CH2:1]([S:3][CH2:4][CH:5]([OH:8])[CH2:6][NH2:7])[CH3:2].[CH:9](=O)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O>C1C=CC=CC=1>[C:10]1([CH:9]2[NH:7][CH2:6][CH:5]([CH2:4][S:3][CH2:1][CH3:2])[O:8]2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1
Reactant: CCSCC(O)CN
Reactant: O=Cc1ccccc1
Solvent: O
Solvent: c1ccccc1
Product: CCSCC1CNC(c2ccccc2)O1
Temperature: 25 °C

Procedure:
Thirteen and five tenths (13.5) grams of 2-hydroxy-3-aminopropyl ethyl sulfide and 10.6 grams of benzaldehyde were combined in 100 milliliters of benzene and refluxed under a modified Dean-Stark apparatus until about 2 milliliters of water had been azetropically removed. The mixture was cooled to room temperature and the volume adjusted to 89.2 milliliters (4 milliliters=1 gram). Aliquots of this mixture were used in subsequent reactions.
Reaction SMILES: [F:1][C:2]([F:36])([F:35])[C:3]([N:5]([CH2:21][CH:22]1[CH2:27][CH2:26][N:25](C(OC(C)(C)C)=O)[CH2:24][CH2:23]1)[C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=2)=[CH:11][CH:10]=1)=[O:4].C(O)(C(F)(F)F)=O>ClCCl>[F:35][C:2]([F:1])([F:36])[C:3]([N:5]([C@@H:6]1[CH2:8][C@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([C:15]2[CH:16]=[N:17][N:18]([CH3:20])[CH:19]=2)=[CH:11][CH:10]=1)[CH2:21][CH:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1)=[O:4]
Reactant: Cn1cc(-c2ccc([C@@H]3C[C@H]3N(CC3CCN(C(=O)OC(C)(C)C)CC3)C(=O)C(F)(F)F)cc2)cn1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: Cn1cc(-c2ccc([C@@H]3C[C@H]3N(CC3CCNCC3)C(=O)C(F)(F)F)cc2)cn1
Temperature: 25 °C
Reaction time: 3 h
Yield: 96.4 %

Procedure:
To a solution of tert-butyl 4-((2,2,2-trifluoro-N-(trans-2-(4-(1-methyl-1H-pyrazol-4-yl)phenyl)cyclopropyl)acetamido)methyl)piperidine-1-carboxylate (110 mg, 0.217 mmol) in dichloromethane (DCM) (2 mL) was added TFA (0.5 mL, 6.49 mmol), and the mixture was stirred at room temperature for 3 h. The mixture was concentrated and the residue was treated with saturated NaHCO3 aqueous solution and extracted with DCM (3×). The extract was dried (Na2SO4) and concentrated to give 85 mg of product as pale yellow solid. MS: (M+H)+=407.2. 1H NMR (400 MHz, METHANOL-d4) δ ppm 1.41-1.54 (m, 2H), 1.58-1.81 (m, 3H), 2.40-2.52 (m, 1H), 2.56-2.69 (m, 2H), 3.06-3.20 (m, 3H), 3.44-3.62 (m, 2H), 3.92-3.97 (m, 3H), 7.13 (d, J=8.34 Hz, 2H), 7.47-7.52 (m, 2H), 7.77-7.82 (m, 1H), 7.92-7.96 (m, 1H).
Reaction SMILES: O(CC)C([S:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]#[N:12])=[CH:7][CH:6]=1)=S.[OH-].[K+]>C(O)C>[C:11]([C:8]1[CH:9]=[CH:10][C:5]([SH:4])=[CH:6][CH:7]=1)#[N:12]
Reactant: CCOC(=S)Sc1ccc(C#N)cc1
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Product: N#Cc1ccc(S)cc1
Yield: 30 %

Procedure:
The ethyl 4-cyanophenyl xanthate was dissolved in ethanol (500 ml) and the solution was refluxed. Potassium hydroxide (112 g, 2 m) was added slowly to the resulting hot solution. Thereafter, the reaction mixture solution was refluxed for approximately three hours. The ethanol was distilled off from the reaction mixture and water (100 ml) was added. The reaction mixture was acidified with 6 N sulfuric acid and the reaction product was extracted with ether. The extract was washed with water and dried over anhydrous sodium sulfate. The solvent was evaporated and the reaction product was vacuum-distilled to yield 4-cyanobenzenethiol (20 g, 30%), bp 102°-103° C./2 mm.
Reaction SMILES: [OH:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH2:12][N:13]3[CH2:18][CH2:17][O:16][CH2:15][CH2:14]3)[CH:10]=2)[N:5]=[N:4][C:3]=1[C:19]([O:21]CC)=O.[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH2:30])=[CH:27][CH:26]=1>CCOCC>[Cl:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][NH:30][C:19]([C:3]2[N:4]=[N:5][C:6]3[C:11]([C:2]=2[OH:1])=[CH:10][C:9]([CH2:12][N:13]2[CH2:14][CH2:15][O:16][CH2:17][CH2:18]2)=[CH:8][CH:7]=3)=[O:21])=[CH:27][CH:26]=1
Reactant: NCc1ccc(Cl)cc1
Reactant: CCOC(=O)c1nnc2ccc(CN3CCOCC3)cc2c1O
Solvent: CCOCC
Product: O=C(NCc1ccc(Cl)cc1)c1nnc2ccc(CN3CCOCC3)cc2c1O
Yield: 89 %

Procedure:
A solution of ethyl 4-hydroxy-6-(4-morpholinylmethyl)-3-cinnolinecarboxylate (Preparation 11, 0.382 g) and 4-chlorobenzylamine (1.46 mL) is heated to 80° C. for 30 min over which time a solid forms. The reaction is diluted with Et2O and the resulting solid is collected and dried to yield 0.443 g (89%) of the desired compound as an off-white solid. Physical characteristics are as follows: m.p. 277-280° C. (dec); 1H NMR (DMSO-d6) δ10.12, 8.09, 7.86, 7.74, 7.40, 4.56, 3.63, 3.58, 2.38; MS (ESI+) for C21H21ClN4O3 m/z 413.0 (M+H)+MS (ESI−), 410.9 (M−H)−.
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]([C:12]2([C:36]([F:39])([F:38])[F:37])[O:16][N:15]=[C:14]([C:17]3[CH:22]=[CH:21][C:20]([CH2:23][N:24]4C(=O)C5=CC=CC=C5C4=O)=[C:19]([Cl:35])[CH:18]=3)[CH2:13]2)[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.O.NN>C(O)C>[NH2:24][CH2:23][C:20]1[CH:21]=[CH:22][C:17]([C:14]2[CH2:13][C:12]([C:4]3[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=[C:2]([Br:1])[CH:3]=3)([C:36]([F:37])([F:38])[F:39])[O:16][N:15]=2)=[CH:18][C:19]=1[Cl:35]
Reactant: O=C1c2ccccc2C(=O)N1Cc1ccc(C2=NOC(c3cc(Br)cc(C(F)(F)F)c3)(C(F)(F)F)C2)cc1Cl
Agent: NN
Solvent: O
Solvent: CCO
Product: NCc1ccc(C2=NOC(c3cc(Br)cc(C(F)(F)F)c3)(C(F)(F)F)C2)cc1Cl
Temperature: 25 °C

Procedure:
To a solution of 5.26 g of N-[[4-[5-[3-bromo-5-(trifluoromethyl)phenyl]-5-trifluoromethyl-4,5-dihydroisoxazole-3-yl]-2-chlorophenyl]methyl]phthalimide in 20 mL of ethanol, 0.73 g of a hydrazine monohydrate aqueous solution was added and the resultant mixture was stirred while heating the mixture to reflux for 1 hour. After the completion of the reaction, the reaction mixture was left to be cooled down to room temperature and from the reaction mixture, an insoluble substance was filtered off and the solvent was distilled off under reduced pressure. To the resultant residue, 20 mL of chloroform was added to dissolve the residue and an insoluble substance was filtered off one more time. The resultant filtrate was washed with water (10 mL×1) and then dehydrated and dried over saturated saline and anhydrous sodium sulfate in this order, and the solvent was distilled off under reduced pressure. The resultant residue was purified by silica gel column chromatography eluting with methanol-ethyl acetate (1:9) to obtain 2.87 g of the objective substance as a yellow resinoid.
Reaction SMILES: [CH:1]1([N:10]2[CH:17]=[CH:16][C:14]([NH2:15])=[N:13][C:11]2=[O:12])[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[C@@H:2]1[OH:3].C1(C)C=CC=CC=1.C(=O)([O-])O.[Na+].[CH2:30]([O:41][C:42](Cl)=[O:43])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]>CC(N(C)C)=O>[CH2:30]([O:41][C:42]([NH:15][C:14]1[CH:16]=[CH:17][N:10]([C@@H:1]2[O:7][C@H:6]([CH2:8][OH:9])[C@@H:4]([OH:5])[C@@H:2]2[OH:3])[C:11](=[O:12])[N:13]=1)=[O:43])[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH2:39][CH3:40]
Reactant: Nc1ccn(C2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)n1
Reactant: CCCCCCCCCCCOC(=O)Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: Cc1ccccc1
Solvent: CC(=O)N(C)C
Product: CCCCCCCCCCCOC(=O)Nc1ccn([C@@H]2O[C@H](CO)[C@@H](O)[C@@H]2O)c(=O)n1
Temperature: 25 °C
Reaction time: 3 h
Yield: 30.4 %

Procedure:
In 130 ml of dimethylacetamide, 7.3 g of arabinofuranosylcytosine is dissolved and to the resultant solution is added 40 ml of a toluene solution containing 7.56 g of sodium hydrogen carbonate and 7.0 g of undecyloxycarbonyl chloride. The mixture is then stirred at room temperature for 3 hours. After the reaction is over, the solvent is removed under reduced pressure and ice-water is added to the residue, whereby the cyrstals are precipitated. The crystals are filtered and washed with water, followed by sufficient drying. Recrystallization of the product is performed twice, using 80 ml of chloroform-n-hexane, to give 4.0 g of N4-undecyloxycarbonyl-1-β-D-arabinofuranosylcytosine (Yield:30%).
Reaction SMILES: BrCCBr.[CH3:5][O:6][C:7](=[O:16])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][Br:15])=[CH:10][CH:9]=1.S([C:27]#[N:28])(C1C=CC(C)=CC=1)(=O)=O>C1COCC1.[Zn].Cl[Si](C)(C)C>[CH3:5][O:6][C:7](=[O:16])[C:8]1[CH:13]=[CH:12][C:11]([CH2:14][Br:15])=[C:10]([C:27]#[N:28])[CH:9]=1
Reactant: Cc1ccc(S(=O)(=O)C#N)cc1
Reactant: COC(=O)c1ccc(CBr)cc1
Agent: C[Si](C)(C)Cl
Agent: [Zn]
Solvent: BrCCBr
Solvent: C1CCOC1
Product: COC(=O)c1ccc(CBr)c(C#N)c1
Temperature: 70 °C
Reaction time: 0.17 h
Yield: 44.6 %

Procedure:
A suspension of zinc dust (792 mg, 12.12 mmol) and 1,2-dibromoethane (44 μL, 0.51 mmol) in THF (3 mL) was stirred at 70° C. for 10 minutes. The mixture was cooled to room temperature and chlorotrimethylsilane (45 μL, 0.36 mmol) was added. The mixture was cooled to 0° C. and a solution of methyl-4(bromomethyl)benzoate (2.314 g, 10.10 mmol) in THF (11 mL) was added at 0° C. over 2 hours and then stirred for an additional 2 hours at 0° C. The reaction mixture was cooled to −78° C. and a solution of tosyl cyanide (1.556 g, 8.59 mmol) in THF (11 mL) was added and the resultant mixture stirred at room temperature for 16 hours. The mixture was concentrated under reduced pressure, diluted with CH2Cl2 (100 mL) and saturated aqueous NaHCO3 (15 mL) and filtered. The phases were separated and the aqueous layer was extracted with CH2Cl2 (3×50 mL). The combined organic extracts were dried (MgSO4), filtered and concentrated under reduced pressure. Purification by column chromatography on silica gel (Hexanes/EtOAc, 10:1) afforded the desired nitrile (973 mg) as a 16:1 mixture (desired product/side product).
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([OH:13])=O)[CH:5]=[CH:6][C:7]=1[F:8].S(Cl)([Cl:16])=O>C1(C)C=CC=CC=1.N1C=CC=CC=1>[F:1][C:2]1[CH:3]=[C:4](/[CH:9]=[CH:10]/[C:11]([Cl:16])=[O:13])[CH:5]=[CH:6][C:7]=1[F:8]
Reactant: O=S(Cl)Cl
Reactant: O=C(O)/C=C/c1ccc(F)c(F)c1
Solvent: Cc1ccccc1
Solvent: c1ccncc1
Product: O=C(Cl)/C=C/c1ccc(F)c(F)c1
Temperature: 65 °C
Reaction time: 0.25 h
Yield: 99.8 %

Procedure:
A stirred mixture of (E)-3-(3,4-difluorophenyl)-2-propenoic acid (8.2 kg), toluene (7.4 kg) and pyridine (0.18 kg) was heated to 65° C. and then thionyl chloride (7.4 kg) was added over 30 minutes. The reaction was stirred for a further 2 h 15 minutes after the addition was complete, then diluted with toluene (8.7 kg). Excess thionyl chloride, sulfur dioxide and hydrogen chloride were then distilled out, together with toluene (10 L), under reduced pressure, yielding a solution of the (E)-3-(3,4-difluorophenyl)-2-propenoyl chloride (approximately 9 kg) in toluene.
Reaction SMILES: [Cl:1][C:2]1[CH:22]=[C:21]([CH3:23])[C:5]([O:6][C:7]2[C:12]([CH3:13])=[C:11]([CH:14]([OH:19])[C:15]([F:18])([F:17])[F:16])[CH:10]=[C:9]([CH3:20])[N:8]=2)=[C:4]([CH3:24])[CH:3]=1.[CH2:25]([N:28]=[C:29]=[O:30])[CH2:26][CH3:27].CN(C1C=CC=CN=1)C>ClCCl>[Cl:1][C:2]1[CH:22]=[C:21]([CH3:23])[C:5]([O:6][C:7]2[C:12]([CH3:13])=[C:11]([CH:14]([O:19][C:29](=[O:30])[NH:28][CH2:25][CH2:26][CH3:27])[C:15]([F:16])([F:17])[F:18])[CH:10]=[C:9]([CH3:20])[N:8]=2)=[C:4]([CH3:24])[CH:3]=1
Reactant: CCCN=C=O
Reactant: Cc1cc(C(O)C(F)(F)F)c(C)c(Oc2c(C)cc(Cl)cc2C)n1
Agent: CN(C)c1ccccn1
Solvent: ClCCl
Product: CCCNC(=O)OC(c1cc(C)nc(Oc2c(C)cc(Cl)cc2C)c1C)C(F)(F)F

Procedure:
A mixture of 1-[2-(4-chloro-2,6-dimethyl-phenoxy)-3,6-dimethyl-pyridin-4-yl]-2,2,2-trifluoro-ethanol (21 mg, 0.0589 mmol), propyl isocyanate (0.1 ml), dimethylaminopyridine (20 mg) in dichloromethane (2 ml) was heated at reflux for 6 hrs. The mixture was quenched with water and extracted with chloroform. The organic layer was separated, dried and concentrated to give 23 mg of yellow solid. The solid was purified by preparative thin layer chromatography (run in 20% ethyl acetate in hexane) to give the title compound as a white solid.
Reaction SMILES: [CH2:1]([NH2:7])[C:2]1[O:6][CH:5]=[CH:4][CH:3]=1.[C:8]([O:12][CH3:13])(=[O:11])[CH:9]=[CH2:10]>>[CH3:13][O:12][C:8]([CH2:9][CH2:10][N:7]([CH2:1][C:2]1[O:6][CH:5]=[CH:4][CH:3]=1)[CH2:10][CH2:9][C:8]([O:12][CH3:13])=[O:11])=[O:11]
Reactant: C=CC(=O)OC
Reactant: NCc1ccco1
Product: COC(=O)CCN(CCC(=O)OC)Cc1ccco1

Procedure:
48.56 Grams of furfurylamine and 200 milliliters of methyl acrylate are refluxed together for 84 hours. The excess methyl acrylate is evaporated off to give 133.46 grams of N,N-di(2-methoxycarbonylethyl)furfurylamine.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2.[O-:13][C:14]#[N:15].[Na+]>C(O)(=O)C.O>[NH:1]([C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[NH:8][C:7](=[O:12])[CH2:6][CH2:5]2)[C:14]([NH2:15])=[O:13]
Reactant: Nc1ccc2c(c1)CCC(=O)N2
Reactant: N#C[O-]
Agent: [Na+]
Solvent: CC(=O)O
Solvent: O
Product: NC(=O)Nc1ccc2c(c1)CCC(=O)N2
Temperature: 25 °C
Yield: 22.2 %

Procedure:
6-Amino-3,4-dihydrocarbostyril (1.6 g) is dissolved in a mixture of acetic acid (5 ml) and water (10 ml), and thereto is added dropwise a solution of sodium cyanate (1.3 g) in water (9 ml) with stirring at room temperature. The mixture is stirred at the same temperature for 1 hour. After the reaction, the resulting precipitate is separated by filtration, washed with water, purified by silica gel column chromatography (solvent; chloroform:methanol=50:1), and recrystallized from dimethylformamide-water to give 6-ureido-3,4-dihydrocarbostyril (0.45 g) as colorless needles, m.p.>300° C.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:24])([CH3:23])[CH3:22])[C:15]3[C:14](=[O:25])[N:13]([CH2:26][CH2:27][CH3:28])[CH:12]=[N:11][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:36][C:37]#[C:38][C:39]1[CH:44]=[CH:43][C:42]([F:45])=[CH:41][CH:40]=1>CC(C)=O>[F:45][C:42]1[CH:43]=[CH:44][C:39]([C:38]#[C:37][CH2:36][O:1][C:2]2[CH:3]=[CH:4][C:5]([C:8]3[N:16]([CH2:17][O:18][CH2:19][CH2:20][Si:21]([CH3:23])([CH3:22])[CH3:24])[C:15]4[C:14](=[O:25])[N:13]([CH2:26][CH2:27][CH3:28])[CH:12]=[N:11][C:10]=4[N:9]=3)=[CH:6][CH:7]=2)=[CH:40][CH:41]=1
Reactant: CCCn1cnc2nc(-c3ccc(O)cc3)n(COCC[Si](C)(C)C)c2c1=O
Reactant: Fc1ccc(C#CCBr)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CCCn1cnc2nc(-c3ccc(OCC#Cc4ccc(F)cc4)cc3)n(COCC[Si](C)(C)C)c2c1=O
Temperature: 80 °C
Yield: 24.8 %

Procedure:
A mixture of 8-(4-hydroxy-phenyl)-1-propyl-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one (0.100 g, 0.25 mmol), potassium carbonate (0.086 g, 0.50 mmol), 1-(3-bromo-prop-1-ynyl)-4-fluoro-benzene (0.107 g, 0.50 mmol) were taken in acetone (10 ml). The reaction mixture was heated at 80° C. for 2 hour. The mixture was cooled to room temperature and filtered through sintered funnel, washed with acetone. Solvent was evaporated and the residue was purified by preparative TLC to obtain pure 8-{4-[3-(4-fluoro-phenyl)-prop-2-ynyloxy]-phenyl}-1-propyl-7-(2-trimethylsilanyl-ethoxymethyl)-1,7-dihydro-purin-6-one (0.033 g, 25%) as pale yellow solid.
Reaction SMILES: [OH-].[K+].O.[C:4]1([SH:10])[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[C:11]1([N:17]2[CH2:22][C:21]3[C:23]4[C:32]([C:33](Cl)=[CH:34][C:20]=3[N:19]=[CH:18]2)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=4)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1>CN(C)C=O>[C:11]1([N:17]2[CH2:22][C:21]3[C:23]4[C:32]([C:33]([S:10][C:4]5[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=5)=[CH:34][C:20]=3[N:19]=[CH:18]2)=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:24]=4)[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: Sc1ccccc1
Reactant: Clc1cc2c(c3cc4ccccc4cc13)CN(c1ccccc1)C=N2
Agent: [K+]
Agent: [OH-]
Solvent: CN(C)C=O
Solvent: O
Product: C1=Nc2cc(Sc3ccccc3)c3cc4ccccc4cc3c2CN1c1ccccc1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
A solution of 40 parts of potassium hydroxide in 60 parts of water is added to a solution of 66 parts of thiophenol in 1,000 parts of dimethylformamide and 171 parts of 2-phenyl-6-chloroanthrapyrimidine are then introduced. The mixture is stirred for 16 hours at room temperature and afterwards for a further hour at 50°-60°C. After cooling to room temperature, the colorant, which has precipitated in orange crystalline platelets, is filtered off, washed with DMF and alcohol and dried at 80°-90°C in vacuo. 194 parts (93.2% of theory) are obtained of 2-phenyl-6-phenylmercaptoanthrapyrimidine, which dyes polyester in bulk in fast, yellow shades.