Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH2:1][C:2]1[C:7](Br)=[CH:6][C:5]([CH3:9])=[CH:4][N:3]=1.[Cu][C:11]#[N:12].C(OCC)(=O)C.[OH-].[Na+]>CN(C=O)C.O>[NH2:1][C:2]1[C:7]([C:11]#[N:12])=[CH:6][C:5]([CH3:9])=[CH:4][N:3]=1
Reactant: Cc1cnc(N)c(Br)c1
Reactant: N#C[Cu]
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: O
Solvent: CN(C)C=O
Product: Cc1cnc(N)c(C#N)c1
Temperature: 180 °C
Reaction time: 0.5 h
Yield: 13.4 %

Procedure:
To a solution of 2-amino-3-bromo-5-methylpyridine (3.74 g) in DMF (30 mL) was added copper(I) cyanide (4.48 g), and the mixture was stirred under microwave irradiation at 180° C. for 30 min. To the reaction mixture were added ethyl acetate and water, 1N aqueous sodium hydroxide solution (50 mL) was added and the mixture was stirred. Insoluble material was filtered off through celite. The aqueous layer and organic layer were separated, and the aqueous layer was extracted with ethyl acetate. The extract was collected, washed with saturated brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (357 mg) as a colorless solid.
Reaction SMILES: O[C:2]1[C:11]2[C:6](=[C:7]([CH3:14])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:17]>>[Cl:17][C:2]1[C:11]2[C:6](=[C:7]([CH3:14])[C:8]([O:12][CH3:13])=[CH:9][CH:10]=2)[N:5]=[CH:4][CH:3]=1
Reactant: COc1ccc2c(O)ccnc2c1C
Reactant: O=P(Cl)(Cl)Cl
Product: COc1ccc2c(Cl)ccnc2c1C
Temperature: 25 °C
Yield: 92.6 %

Procedure:
A solution of 4-hydroxy-7-methoxy-8-methylquinoline (59, 6.4 g, 33.8 mmol) in POCl3 (17.2 g, 111.6 mmol) was heated at reflux for 1 h under nitrogen. Then, the resulting solution was cooled down to room temperature and the excess of POCl3 was evaporated under reduced pressure. The residue was partitioned between ice-cold 1N NaOH and AcOEt. The organic layer was dried (Na2SO4), and evaporated. The residue was purified by silica-gel filtration (AcOEt/CH2Cl2/Heptane, 4:4:2) to give 6.5 g (92.5%) of the target product 60 as yellow needles: m/z=208 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[C:10]2[CH:9]([CH2:11][C:12]([O:14]CC)=[O:13])[O:8][B:7]([OH:17])[C:6]=2[CH:5]=[C:4]([O:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[CH:3]=1.[OH-].[Li+].Cl>C1COCC1.O>[Cl:1][C:2]1[C:10]2[CH:9]([CH2:11][C:12]([OH:14])=[O:13])[O:8][B:7]([OH:17])[C:6]=2[CH:5]=[C:4]([O:18][C:19]2[CH:24]=[N:23][CH:22]=[CH:21][N:20]=2)[CH:3]=1
Reactant: CCOC(=O)CC1OB(O)c2cc(Oc3cnccn3)cc(Cl)c21
Agent: Cl
Agent: [Li+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: O
Product: O=C(O)CC1OB(O)c2cc(Oc3cnccn3)cc(Cl)c21
Temperature: 0 °C
Reaction time: 2 h
Yield: 66.1 %

Procedure:
To the solution of ethyl 2-(4-chloro-1-hydroxy-6-(pyrazin-2-yloxy)-1,3-dihydrobenzo[c][1,2]oxaborol-3-yl)acetate (110 mg, 0.316 mmol) in THF (2 mL) was added an aqueous solution of lithium hydroxide (66 mg, 1.58 mmol) in water (1 mL) at 0° C. The resulting mixture was stirred at 0° C. for 2 h, acidified with diluted hydrochloric acid at 0° C. to pH=1˜2 and extracted with EtOAc (2×20 mL). The combined organic layers were dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by prep HPLC to give the title compound as a white powder (66.9 mg, Yield: 83.5%). 1H NMR (400 MHz, DMSO-d6)δ 9.51 (s, 1H), 8.61 (s, 1H), 8.43 (s, 1H), 8.24 (s, 1H), 7.53 (s, 1H), 7.47 (s, 1H), 5.53-5.55 (d, J=8.4 Hz, 1H), 3.23-3.36 (d, J=15.6 Hz, 1H), 2.33-2.40 (m, 1H); MS (ESI) m/z=321 [M+H]+.
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[CH:14]=[O:15])=[O:4].[BH4-].[Na+]>CO>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][N:9]=[C:8]2[CH2:14][OH:15])=[O:4]
Reactant: COC(=O)c1ccc2[nH]nc(C=O)c2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: COC(=O)c1ccc2[nH]nc(CO)c2c1
Temperature: 0 °C
Reaction time: 0.5 h

Procedure:
To a solution of 3-formyl-1H-indazole-5-carboxylic acid methyl ester (0.37 g, 1.80 mmol) in anhydrous methanol (15 mL) was added sodium borohydride (68 mg, 1.80 mmol) in small portions at 0° C. After the addition, the reaction mixture was stirred at 0° C. for 30 minutes. Solvent was evaporated; water (100 mL) was added and the mixture was extracted with ethyl acetate (150 mL). The organic phase was washed with brine (100 mL) and dried over anhydrous Na2SO4. Solvent was evaporated to give 3-hydroxymethyl-1H-indazole-5-carboxylic acid methyl ester as a yellow solid. Yield: 0.32 g (87%).
Reaction SMILES: Br[CH2:2][C:3]1[CH:4]=[C:5]([Cl:10])[C:6]([Cl:9])=[N:7][CH:8]=1.[C:11]1(=[O:21])[NH:15][C:14](=[O:16])[C:13]2=[CH:17][CH:18]=[CH:19][CH:20]=[C:12]12.[K].O>CN(C=O)C>[Cl:10][C:5]1[CH:4]=[C:3]([CH2:2][N:15]2[C:11](=[O:21])[C:12]3[C:13](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:14]2=[O:16])[CH:8]=[N:7][C:6]=1[Cl:9]
Reactant: O=C1NC(=O)c2ccccc21
Reactant: Clc1cc(CBr)cnc1Cl
Agent: [K]
Solvent: CN(C)C=O
Solvent: O
Product: O=C1c2ccccc2C(=O)N1Cc1cnc(Cl)c(Cl)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A mixture of 5-bromomethyl-2,3-dichloro-pyridine from step (a) above (121 mg, 0.5 mmol) and potassium phthalimide (139 mg, 0.75 mmol, Aldrich) in DMF (1 mL) was stirred at room temperature for 30 min. Water (5 mL) was added and the mixture was extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (5 mL) and brine (5 mL), dried over Na2SO4, and filtered. The filtrate was evaporated in vacuo and the residue was suspended in 20% EtOAc/hexane, and filtered. The solid was washed with 20% EtOAc/hexane and dried in vacuo to give the title compound. MS (ESI, pos. ion) m/z: 307 (M+1).
Reaction SMILES: [NH2:1][CH2:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[C:5]([I:14])[CH:4]=1.Cl.C1([O:22][C:23](=O)[NH:24][CH2:25][C:26]2[CH:31]=[CH:30][C:29]([C:32]([CH3:35])([CH3:34])[CH3:33])=[CH:28][CH:27]=2)C=CC=CC=1>>[C:32]([C:29]1[CH:30]=[CH:31][C:26]([CH2:25][NH:24][C:23](=[O:22])[NH:1][CH2:2][C:3]2[CH:8]=[CH:7][C:6]([NH:9][S:10]([CH3:13])(=[O:12])=[O:11])=[C:5]([I:14])[CH:4]=2)=[CH:27][CH:28]=1)([CH3:35])([CH3:33])[CH3:34]
Reactant: CC(C)(C)c1ccc(CNC(=O)Oc2ccccc2)cc1
Reactant: CS(=O)(=O)Nc1ccc(CN)cc1I
Agent: Cl
Product: CC(C)(C)c1ccc(CNC(=O)NCc2ccc(NS(C)(=O)=O)c(I)c2)cc1

Procedure:
N-(4-Aminomethyl-2-iodo-phenyl)-methanesulfonamide and HCl salt (297 mg, 0.820 mmol) were reacted with (4-t-butyl-benzyl)-carbamic acid phenyl ester following the general procedure to give a white solid (152 mg).
Reaction SMILES: Cl.NO.C([N:6](C(C)C)C(C)C)C.C(OC([NH:18][C:19]([NH:21][C:22]1[CH:27]=[CH:26][C:25]([Br:28])=[CH:24][N:23]=1)=S)=O)C>C(O)C>[Br:28][C:25]1[CH:26]=[CH:27][C:22]2[N:23]([N:6]=[C:19]([NH2:18])[N:21]=2)[CH:24]=1
Reactant: CCN(C(C)C)C(C)C
Reactant: CCOC(=O)NC(=S)Nc1ccc(Br)cn1
Agent: Cl
Agent: NO
Solvent: CCO
Product: Nc1nc2ccc(Br)cn2n1
Temperature: 25 °C
Yield: 85.7 %

Procedure:
A mixture of hydroxylamine hydrochloride (40.0 g, 575 mmol) and N-ethyldiisopropylamine (44.6 g, 60.3 ml, 345 mmol) in ethanol (734 ml) was stirred for a few minutes at 25° C., then the mixture was added to 1-ethoxycarbonyl-3-(5-bromo-pyridin-2-yl)-thiourea (35 g, 115 mmol) and the resulting mixture was refluxed for 1 day. The solvent was evaporated under reduced pressure and the white solid was treated with 400 ml water. The suspension was stirred for 1 hour, the solid was filtered off, washed with water 3 times and dried under reduced pressure, affording 6-bromo-[1,2,4]triazolo[1,5-a]pyridin-2-ylamine (21 g, 85%) as white solid. Mp.: 185° C. MS: m/z=213.0/215.1 (M+H+).
Reaction SMILES: C(O[C:6](=O)[N:7]([CH:9]([CH3:34])[C:10]([NH:12][C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:15]([C:26]#[C:27][C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[N:14]=1)=[O:11])C)(C)(C)C.C(Cl)Cl.C(O)(C(F)(F)F)=O>C(Cl)Cl>[CH2:19]([C:16]1[CH:17]=[CH:18][C:13]([NH:12][C:10](=[O:11])[CH:9]([NH:7][CH3:6])[CH3:34])=[N:14][C:15]=1[C:26]#[C:27][C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1
Reactant: CC(C(=O)Nc1ccc(Cc2ccccc2)c(C#Cc2ccccc2)n1)N(C)C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CNC(C)C(=O)Nc1ccc(Cc2ccccc2)c(C#Cc2ccccc2)n1
Temperature: 25 °C
Reaction time: 1.5 h

Procedure:
A mixture of tert-butyl-N-[1-[[5-benzyl-6-(2-phenylethynyl)pyridin-2-yl]amino]-1-oxopropan-2-yl]-N-methylcarbamate E2d (26 mg, 0.6 mmol) and DCM:TFA (9:1, 2 ml) is stirred at RT for 90 minutes. The mixture is diluted with DCM and extracted with a saturated aqueous solution of NaHCO3. The combined organic layers are dried over MgSO4 and concentrated in vacuo. The product is purified by RP HPLC. Yield: 4 mg (20%). HPLC-MS: M+H=370; tR=2.16 min (*Method—1).
Reaction SMILES: [CH3:1][C:2]1([CH3:25])[C:7]2[CH2:8][CH2:9][CH2:10][C:6]=2[C:5]2[C:11]([OH:24])=[CH:12][C:13]([CH:15]([CH:17]([CH3:23])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH3:16])=[CH:14][C:4]=2[O:3]1.C1(N=C=NC2CCCCC2)CCCCC1.[ClH:41].[N:42]1([CH2:48][CH2:49][CH2:50][C:51](O)=[O:52])[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]1>C(Cl)Cl>[ClH:41].[CH3:25][C:2]1([CH3:1])[C:7]2[CH2:8][CH2:9][CH2:10][C:6]=2[C:5]2[C:11]([O:24][C:51](=[O:52])[CH2:50][CH2:49][CH2:48][N:42]3[CH2:47][CH2:46][CH2:45][CH2:44][CH2:43]3)=[CH:12][C:13]([CH:15]([CH:17]([CH3:23])[CH2:18][CH2:19][CH2:20][CH2:21][CH3:22])[CH3:16])=[CH:14][C:4]=2[O:3]1
Reactant: CCCCCC(C)C(C)c1cc(O)c2c(c1)OC(C)(C)C1=C2CCC1
Reactant: O=C(O)CCCN1CCCCC1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: ClCCl
Product: CCCCCC(C)C(C)c1cc(OC(=O)CCCN2CCCCC2)c2c(c1)OC(C)(C)C1=C2CCC1

Procedure:
5.0 g. (14.6 mmoles) of 4,4-dimethyl-9-hydroxy-7-(3-methyl-2-octyl)-1,2,3,4-tetrahydrocyclopenta[c][ l] benzopyran, 3.14 g. (15.2 mmoles) of dicyclohexylcarbodiimide and 3.15 g. (15.2 mmoles) of γ-piperidinobutyric acid hydrochloride (m.p. 190°-192°), Cruickshank & Sheehan, J. Am. Chem. Soc. 83, 2891 (1961), were combined with 250 ml. of methylene chloride and stirred for a total of 40 hours at room temperature. The insoluble by-product of dicyclohexylurea was separated by filtration and the methylene chloride was removed using a rotary evaporator. The brown residue was treated with approximately 75 ml. of benzene, and filtered to remove a small amount of insoluble material. The benzene was evaporated and the brown viscous residue was triturated with about 200 ml. of ether to give 4.3 g. of crude product as a light brown solid, m.p. 174°-176°. Recrystallization from benzene gave a total of 3.5 g. (45%) of product as colorless crystals, m.p. 174°-176°. The infrared and nmr spectra are in agreement with the proposed structure.
Reaction SMILES: [C:1]1([C:7]2[CH2:13][CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[C:8]=2[C:18]2[CH:23]=[CH:22][C:21](OS(C(F)(F)F)(=O)=O)=[CH:20][CH:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:32](#[N:35])[CH:33]=[CH2:34].C(N(CC)CC)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]1([C:7]2[CH2:13][CH2:12][CH2:11][C:10]3[CH:14]=[CH:15][CH:16]=[CH:17][C:9]=3[C:8]=2[C:18]2[CH:23]=[CH:22][C:21]([CH:34]=[CH:33][C:32]#[N:35])=[CH:20][CH:19]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: C=CC#N
Reactant: O=S(=O)(Oc1ccc(C2=C(c3ccccc3)CCCc3ccccc32)cc1)C(F)(F)F
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: N#CC=Cc1ccc(C2=C(c3ccccc3)CCCc3ccccc32)cc1
Temperature: 100 °C
Yield: 45.8 %

Procedure:
To a solution of triflate (5b) (560 mg, 1.25 mmol) in DMF (6 mL) was added acrylonitrile (2.10 g, 39.6 mmol), triethylamine (2.90 g, 28.6 mmol), and bis(triphenyl-phosphine)palladium(II) chloride (700 mg, 1.0 mmol). The mixture was placed in a pressure bottle and heated at 100° C. for 4 days. The solvent was removed under reduced pressure and the residue chromatographed (silica gel, 15% EtOAc/hexanes) to give nitrile (5c) as a white solid (199 mg, 46%): 1H NMR (CDCl3) δ 7.30–7.13 (m, 11H), 6.94 (d, J=8.1 Hz, 2H), 6.82 (dd, J=7.3, 1.1 Hz, 1H), 5.75 (d, J=16.5 Hz, 1H), 2.81 (t, J=7.0 Hz, 2H), 2.40 (t, J=7.0 Hz, 2H), 2.19 (m, 2H).
Reaction SMILES: [Na:1].CC1(C)COC(C[O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH2:17][S:18]([C:20]3[NH:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[N:21]=3)=[O:19])[C:12]=2[CH3:29])OC1.[CH3:31][C:32]1([CH3:41])[CH2:37][O:36][CH:35]([CH2:38][CH2:39]O)[O:34][CH2:33]1>>[Na:1].[CH3:31][C:32]1([CH3:41])[CH2:37][O:36][CH:35]([CH2:38][CH2:39][O:10][C:11]2[CH:16]=[CH:15][N:14]=[C:13]([CH2:17][S:18]([C:20]3[NH:24][C:23]4[CH:25]=[CH:26][CH:27]=[CH:28][C:22]=4[N:21]=3)=[O:19])[C:12]=2[CH3:29])[O:34][CH2:33]1
Reactant: Cc1c(OCC2OCC(C)(C)CO2)ccnc1CS(=O)c1nc2ccccc2[nH]1
Reactant: CC1(C)COC(CCO)OC1
Agent: [Na]
Product: Cc1c(OCCC2OCC(C)(C)CO2)ccnc1CS(=O)c1nc2ccccc2[nH]1

Procedure:
The same procedure as in the steps (1c) to (1g) of Example 1 was repeated using 5,5-dimethyl-1,3-dioxane-2-ethanol (1.00 g, 6.24 mmol) to obtain the title compound (138 mg, 0.31 mmol) as a beige solid.
Reaction SMILES: Br[C:2]1[CH:6]=[CH:5][S:4][C:3]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.[B:13](OC(C)C)([O:18]C(C)C)[O:14]C(C)C.[Li]CCCC>C1COCC1.Cl>[C:7]1([C:3]2[S:4][CH:5]=[CH:6][C:2]=2[B:13]([OH:18])[OH:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: CC(C)OB(OC(C)C)OC(C)C
Reactant: Brc1ccsc1-c1ccccc1
Agent: Cl
Agent: [Li]CCCC
Solvent: C1CCOC1
Product: OB(O)c1ccsc1-c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 5.1 %

Procedure:
To a mixture of 3-bromo-2-phenylthiophene (1.99 g, 8.32 mmol) and B(Oi-Pr)3 (1.81 mL, 12.5 mmol) in THF (20 mL) was added n-BuLi (1.65 M in hexane, 10.1 mL, 16.6 mmol) at −78° C. The mixture was stirred at −78° C. for 30 min and at 0° C. for 30 min. The mixture was diluted with 1 M HCl aqueous solution at 0° C., extracted with EtOAc, washed with brine, dried over Na2SO4, filtered, concentrated in vacuo and purified by column chromatography on silica gel (hexane/EtOAc=90/10 to 0/100) to yield the title compound (87.4 mg, 5% yield) as a white solid: 1H NMR (DMSO-d6, 300 MHz): δ ppm 7.19 (1H, d, J=4.9 Hz), 7.27-7.44 (3H, m), 7.46-7.58 (3H, m), 8.06 (2H, s).
Reaction SMILES: [N:1]([CH2:4][CH:5]([C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[N:8]=1)[OH:6])=[N+:2]=[N-:3].[C:14](OC=C)(=[O:16])[CH3:15]>C1(C)C=CC=CC=1>[N:1]([CH2:4][C@@H:5]([O:6][C:14](=[O:16])[CH3:15])[C:7]1[CH:12]=[CH:11][CH:10]=[C:9]([CH3:13])[N:8]=1)=[N+:2]=[N-:3]
Reactant: C=COC(C)=O
Reactant: Cc1cccc(C(O)CN=[N+]=[N-])n1
Solvent: Cc1ccccc1
Product: CC(=O)O[C@H](CN=[N+]=[N-])c1cccc(C)n1
Temperature: 25 °C
Reaction time: 4.5 h
Yield: 41.4 %

Procedure:
Dissolved 2-Azido-1-(6-methyl-pyridin-2-yl)-ethanol (4.300 g, 24.130 mmol) into 200 mL of toluene. To this was added vinyl acetate (9.22 mL, 100.00 mmol) and Lipase PS-C II (4.00 g). The mixture stirred for 4.5 h at RT and was monitored by 1H NMR. The reaction mixture was filtered through a bed of celite and rinsed with 100 mL of toluene. The filtrate was concentrated in vacuo. Dissolved residue into CH2Cl2, applied to a SiO2 Column and purified (5–30% EtOAc/hexanes) to give 2.20g of acetic acid (R)-2-azido-1-(6-methyl-pyridin-2-yl)-ethyl ester and 2.11 of (S)-2-azido-1-(6-methyl-pyridin-2-yl)-ethanol, ee % >99.
Reaction SMILES: [CH:1]1[C:18]2=[C:19]3[C:8]([C:9]4[C:20]5[C:13](=[CH:14][CH:15]=[CH:16][C:17]2=5)[CH:12]=[CH:11][CH:10]=4)=[CH:7][CH:6]=[C:5]2[C:21]([O:23][C:24](=O)[C:3](=[C:4]23)[CH:2]=1)=[O:22].[NH2:26][CH:27]([CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].N1C=CN=C1.Cl>O.O.C([O-])(=O)C.[Zn+2].C([O-])(=O)C.C(O)C>[CH2:28]([CH:27]([N:26]1[C:21](=[O:22])[C:5]2[C:4]3[C:19]4[C:8](=[CH:7][CH:6]=2)[C:9]2[C:20]5[C:13]([CH:12]=[CH:11][CH:10]=2)=[CH:14][CH:15]=[CH:16][C:17]=5[C:18]=4[CH:1]=[CH:2][C:3]=3[C:24]1=[O:23])[CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39])[CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: O=C1OC(=O)c2ccc3c4cccc5cccc(c6ccc1c2c63)c54
Reactant: CCCCCCC(N)CCCCCC
Agent: CC(=O)[O-]
Agent: Cl
Agent: [Zn+2]
Solvent: CCO
Solvent: O
Product: CCCCCCC(CCCCCC)N1C(=O)c2ccc3c4cccc5cccc(c6ccc(c2c36)C1=O)c54

Procedure:
200 mg (620 mmol) of perylene-3,4-dicarboxylic anhydride (prepared according to Example 20, below) are heated together with 250 mg (0.12 mmol) of 7-aminotridecane, 110 mg of zinc acetate dihydrate and 1.2 g of imidazole under an argon inert atmosphere at 135°-140° C. for 1 h. After cooling, the dark-red melt cake is digested with 100 ml of ethanol, and 100 ml of 15 per cent hydrochloric acid are added to the resulting suspension, and the mixture is boiled until all the ethanol has evaporated (the reaction product is readily soluble in ethanol). The solid is filtered off with suction and washed with warm water until the filtrate run-off no longer gives a yellow fluorescence. The crude product is then dried in a drying cabinet at 120° C. for 2 h and then chromatographed on silica gel using chloroform. The first coloured fraction is recrystallized by extraction with methanol. Yield 200 mg (63%) orange-red crystals showing strong solid fluorescence, m.p. 166°-168° C. Rf (chloroform/silica gel)=0.87. UV (CHCl3): λmax (ε)=506 (30250), 484 (31580). Fluorescence (CHCl3, exc. 506 nm) λmax (Irel): 540 (1), 568 (0.52).
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]([C:14]([OH:16])=O)[CH3:13])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[C:30]([O:34][C:35](=[O:41])[C@@H:36]1[CH2:40][CH2:39][CH2:38][NH:37]1)([CH3:33])([CH3:32])[CH3:31]>O1CCCC1.C(Cl)(Cl)Cl>[C:30]([O:34][C:35](=[O:41])[C@@H:36]1[CH2:40][CH2:39][CH2:38][N:37]1[C:14](=[O:16])[C@H:12]([CH3:13])[NH:11][C:9]([O:8][CH2:1][C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)=[O:10])([CH3:33])([CH3:31])[CH3:32]
Reactant: CC(C)(C)OC(=O)[C@@H]1CCCN1
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Agent: CCOC(=O)Cl
Solvent: CCN(CC)CC
Solvent: ClC(Cl)Cl
Solvent: C1CCOC1
Product: C[C@H](NC(=O)OCc1ccccc1)C(=O)N1CCC[C@H]1C(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 1 h
Yield: 99.8 %

Procedure:
In 210 ml of tetrahydrofuran is dissolved 26.1 g of N-benzyloxycarbonyl-L-alanine, and a solution of 16.4 ml of triethylamine in 20 ml of tetrahydrofuran is added dropwise to the solution at the temperature below -10° C. with stirring. Then, a solution of 11.2 ml of ethyl chlorocarbonate in 20 ml of tetrahydrofuran is added dropwise to the solution. After stirring for 20 minutes, a solution of 15.4 g of L-proline tert-butyl ester in 102 ml of chloroform is added dropwise to the mixture at the temperature below -10° C. over a period of 48 minutes. After the addition is completed, stirring is continued for 1 hour under cooling and for 1.5 hours at room temperature. The reaction solution is poured into 600 ml of ice-water, and the chloroform layer is separated and concentrated under reduced pressure. The residue is dissolved in 304 ml of ethyl acetate, and the solution is washed with 1N aqueous sodium hydroxide, saturated aqueous sodium chloride, 20% aqueous phosphoric acid and saturated aqueous sodium chloride, successively. The ethyl acetate layer is dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to give 33.8 g of N-(N-benzyloxycarbonyl-L-alanyl)-L-proline tert-butyl ester as an oil. This product is dissolved in 304 ml of methanol containing 8.12 g of oxalic acid, and 10% palladium-carbon (50% wet, 3.6 g) are added to the solution to conduct catalytic reduction at ambient temperature and under atmospheric pressure. The catalyst is filtered off, and the filtrate is concentrated under reduced pressure. 400 ml of ethyl ether is added to the residue, and the crystals which separate out are collected by filtration to give 20.2 g of N-(L-alanyl)-L-proline tert-butyl ester·oxalate as a colorless powder.
Reaction SMILES: [CH3:1][CH:2]([CH2:15][CH3:16])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][OH:14].C(N(CC)CC)C.[C:24](Cl)(=[O:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39].CCCCCC>CN(C)C1C=CN=CC=1.C(OCC)C.C(OCC)(=O)C>[C:24]([O:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][CH2:6][CH2:5][CH2:4][CH2:3][CH:2]([CH3:1])[CH2:15][CH3:16])(=[O:40])[CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH2:37][CH2:38][CH3:39]
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Reactant: CCC(C)CCCCCCCCCCCO
Agent: CN(C)c1ccncc1
Solvent: CCOC(C)=O
Solvent: CCCCCC
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCCCCC(=O)OCCCCCCCCCCCC(C)CC
Temperature: 25 °C
Yield: 84.6 %

Procedure:
A dry 500 ml 3-neck round bottom flask fitted with a condenser is charged with 12-methyltetradecan-1-ol (10.0 g, 0.0438 mol) from example I.A, 125 ml diethyl ether, triethylamine (4.87 g, 0.0481 mol), and 4-(dimethylamino)pyridine (DMAP) 0.5350 g, 0.0044 mol). The solution is stirred at room temperature under a positive N2 atmosphere. Palmitoyl chloride (13.20 g, 0.0481 mol) in 13 ml diethyl ether is added dropwise to the reaction flask from an addition funnel at room temperature. A thick white precipitate forms. An additional 115 ml of diethyl ether is added to help stirring the thick slurry. The mixture is stirred overnight at room temperature under a nitrogen atmosphere. After 18 hours reaction time an aliquot of the mixture is spotted on a TLC plate (95:5 v/v hexane:ethyl acetate) versus the starting materials, indicating the reaction to be complete. The reaction mixture is vacuum filtered, and the filter cake rinsed with 2×400 ml diethyl ether. The filtrate is back extracted with 2×400 ml water. The ether phase is dried with anhydrous magnesium sulfate, vacuum filtered and the filtrate concentrated in vacuo on a rotary evaporator at 40° and the crude product recovered (20.3 g). The crude product is dissolved in warm ethanol (150 ml) and placed into a freezer to recrystallize the product. The precipitated product is vacuum filtered and the filter cake rinsed with 0° C. ethanol (3×50 ml). The cake is further dried in vacuo at room temperature to yield 12-methyltetradecyl palmitate as a white powdery solid (17.3 g). Yield 84.1%.
Reaction SMILES: [N:1]1([C:7]2[C:8]3[N:9]([CH:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:20]=3)[C:10]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][N:12]=2)[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.[CH3:26]O.C=O>C(Cl)Cl>[CH3:26][N:4]1[CH2:3][CH2:2][N:1]([C:7]2[C:8]3[N:9]([CH:18]=[C:19]([C:21]([O:23][CH2:24][CH3:25])=[O:22])[N:20]=3)[C:10]([C:13]3[S:14][CH:15]=[CH:16][CH:17]=3)=[CH:11][N:12]=2)[CH2:6][CH2:5]1
Reactant: CO
Reactant: CCOC(=O)c1cn2c(-c3cccs3)cnc(N3CCNCC3)c2n1
Agent: C=O
Solvent: ClCCl
Product: CCOC(=O)c1cn2c(-c3cccs3)cnc(N3CCN(C)CC3)c2n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 72 %

Procedure:
A 25 mL round bottom flask was charged with ethyl 8-(piperazin-1-yl)-5-(thiophen-2-yl)imidazo[1,2-a]pyrazine-2-carboxylate (200 mg, 0.56 mmol), MeOH (15 mL), CH2Cl2 (15 mL), 40% aqueous formaldehyde (1 mL) and NaBH3(CN) (250 mg, 3.9 mmol). The mixture was stirred at 25° C. for 1 h. Reaction progress was monitored by LC-MS. Work-up: the solvent was evaporated. The residue was purified by flash column chromatography on silica gel with a 1:20 MeOH/CH2Cl2, to afford 150 mg (72%) of the product. 1H NMR (300 MHz, CDCl3) δ: 8.33 (s, 1H), 7.50 (s, 1H), 7.48 (dd, J=5.4, 1.2 Hz, 1H), 7.35 (dd, J=3.3, 1.2 Hz, 1H), 7.20 (dd, J=5.4, 3.3 Hz, 1H), 4.43-4.38 (m, 6H), 2.59 (t, J=5.1 Hz, 4H), 1.40 (t, J=6.9 Hz, 3H). MS m/z: 372 (M+H+).