Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:7]2[N:8]=[C:9](C)[CH:10]=[C:6]2[N:5]=[C:4]([NH:12][C:13](=[O:24])[C:14]2[CH:19]=[CH:18][C:17]([C:20]([OH:23])([CH3:22])[CH3:21])=[CH:16][CH:15]=2)[CH:3]=1.[NH:25]1[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26]1>O1CCOCC1.CS(C)=O.CO>[OH:23][C:20]([C:17]1[CH:18]=[CH:19][C:14]([C:13]([NH:12][C:4]2[CH:3]=[C:2]([N:25]3[CH2:29][CH2:28][CH:27]([OH:30])[CH2:26]3)[N:7]3[N:8]=[CH:9][CH:10]=[C:6]3[N:5]=2)=[O:24])=[CH:15][CH:16]=1)([CH3:22])[CH3:21]
Reactant: Cc1cc2nc(NC(=O)c3ccc(C(C)(C)O)cc3)cc(Cl)n2n1
Reactant: OC1CCNC1
Solvent: C1COCCO1
Solvent: CO
Solvent: CS(C)=O
Product: CC(C)(O)c1ccc(C(=O)Nc2cc(N3CCC(O)C3)n3nccc3n2)cc1
Temperature: 25 °C
Yield: 22.8 %

Procedure:
A solution of N-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)-4-(2-hydroxypropan-2-yl)benzamide (2D, 200 mg, 0.604 mmol) and pyrrolidin-3-ol (80 mg, 0.906 mmol) in Dioxane (6 mL) was stirred at 85° C. overnight. After cooling to room temperature, the mixture was diluted with a few drops of DMSO and methanol, and was then purified by preparatory HPLC, 5-95% (MeCN/H2O gradient+0.01% TFA). Lyophilization of the combined fractions gave the titled compound as a white solid (52.5 mg, 23%). 1H NMR (400 MHz, DMSO-d6) δ: 10.63 (s, 1H), 7.82-8.10 (m, 3H), 7.58 (d, 2H), 7.05 (s, 1H), 6.17 (d, J=2.3 Hz, 1H), 5.17 (s, 1H), 5.10 (d, J=3.3 Hz, 1H), 4.43 (br. s., 1H), 3.87-4.13 (m, 4H), 1.87-2.12 (m, 2H), 1.45 (s, 6H). ESI-MS: m/z 382.0 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:19])([F:18])[F:17])[N:11]([CH3:20])[C:10]2=[O:21])=[C:4](F)[C:3]=1[N+:23]([O-:25])=[O:24].C([O-])(=[O:28])C.[Na+]>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([N:9]2[C:14](=[O:15])[CH:13]=[C:12]([C:16]([F:18])([F:17])[F:19])[N:11]([CH3:20])[C:10]2=[O:21])=[C:4]([OH:28])[C:3]=1[N+:23]([O-:25])=[O:24]
Reactant: CC(=O)[O-]
Reactant: Cn1c(C(F)(F)F)cc(=O)n(-c2c(F)cc(Cl)c([N+](=O)[O-])c2F)c1=O
Agent: [Na+]
Solvent: CN(C)C=O
Product: Cn1c(C(F)(F)F)cc(=O)n(-c2c(F)cc(Cl)c([N+](=O)[O-])c2O)c1=O
Temperature: 100 °C

Procedure:
30 g of 3-[4-chloro-2,6-difluoro-3-nitrophenyl]-1-methyl-6-trifluoromethyl-2,4-(1H,3H)-pyrimidinedione were dissolved in 100 ml of absolute dimethylformamide, admixed with 25.2 g of sodium acetate and heated at 100° C. for four hours. After cooling, the solvent was removed under reduced pressure and the residue was admixed with water; by addition of dilute hydrochloric acid, the pH was taken into the acidic range, and the mixture was extracted with methyl tert-butyl ether (three times 75 ml). The product of value was obtained as a mixture with the isomer formed by exchange of the fluorine atom which is in the position para to the nitro group. Total yield: 28.3 g. The crude product was purified at the subsequent stage (intermediate 7).
Reaction SMILES: COC1C=CC(C([NH:9][C:10]2([C:20]3[CH:25]=[CH:24][C:23]([C:26]([F:29])([F:28])[F:27])=[CH:22][CH:21]=3)[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[O:13][CH2:12][CH2:11]2)=O)=CC=1.Cl>>[F:29][C:26]([F:27])([F:28])[C:23]1[CH:22]=[CH:21][C:20]([C@:10]2([NH2:9])[C:15]3=[N:16][CH:17]=[CH:18][CH:19]=[C:14]3[O:13][CH2:12][CH2:11]2)=[CH:25][CH:24]=1
Reactant: COc1ccc(C(=O)NC2(c3ccc(C(F)(F)F)cc3)CCOc3cccnc32)cc1
Agent: Cl
Product: N[C@]1(c2ccc(C(F)(F)F)cc2)CCOc2cccnc21
Temperature: 150 °C

Procedure:
To a microwave vial with 4-methoxy-N-(4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-yl)benzamide (2 g, 4.67 mmol) was added HCl (5 M aqueous, 20 mL, 100 mmol). The vial was sealed and heated by microwave at 150° C. for 80 min. The reaction was then concentrated in vacuo and the residue dissolved in half saturated aqueous NaHCO3 (75 mL) and DCM (50 mL). The organic layer was separated, and the aqueous layer was extracted with DCM (2×50 mL). The combined organic layers were washed with brine, dried over MgSO4, and concentrated to give a green oil. Purification by ISCO (40 g SiO2, 10-100% acetone in hexanes) gave racemic title compound. 4-(4-(trifluoromethyl)phenyl)-3,4-dihydro-2H-pyrano[3,2-b]pyridin-4-amine ( ) was separated by preparative SFC (using a AD-H (2×15 cm); mobile phase: 12% isopropanol (DEA)/CO2, at a flow rate of 60 mL/min] resulting in Peak 1 and 2 fractions with enantiomeric excess >99%).
Reaction SMILES: [CH2:1]([CH2:10][NH:11][C:12]1[C:20]2[C:15](=[CH:16][C:17]([Cl:22])=[C:18]([Cl:21])[CH:19]=2)[N:14](C(OC(C)(C)C)=O)[C:13]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3].FC(F)(F)C(O)=O>C(Cl)Cl.C(OCC)(=O)C>[CH2:1]([CH2:10][NH:11][C:12]1[C:20]2[C:15](=[CH:16][C:17]([Cl:22])=[C:18]([Cl:21])[CH:19]=2)[NH:14][C:13]=1[C:30]([O:32][CH2:33][CH3:34])=[O:31])[C:2]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)=[O:3]
Reactant: CCOC(=O)c1c(NCCC(=O)c2ccccc2)c2cc(Cl)c(Cl)cc2n1C(=O)OC(C)(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: CCOC(C)=O
Solvent: ClCCl
Product: CCOC(=O)c1[nH]c2cc(Cl)c(Cl)cc2c1NCCC(=O)c1ccccc1

Procedure:
Dissolve 3-[(phenacyl)methylamino]-2-carbethoxy-5,6-dichloro-1-(tert-butyloxycarbonyl)-indole from above in methylene chloride (15 mL). Add trifluoracetic acid (5 mL) and stir for 5 hours. Concentrate the reaction in vacuo, dilute with ethyl acetate (100 mL), wash with saturated sodium carbonate, dry over magnesium sulfate, filter and concentrate in vacuo. Recrystallizethe residue from ethyl acetate/hexane to yield the title compound.
Reaction SMILES: O=P(Cl)(Cl)[Cl:3].[Cl:6][C:7]1[CH:8]=[C:9]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12](=O)[C:11]([C:18]#[N:19])=[C:10]2[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>O>[Cl:3][C:12]1[C:11]([C:18]#[N:19])=[C:10]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[C:9]2[C:14](=[CH:15][CH:16]=[C:7]([Cl:6])[CH:8]=2)[N:13]=1
Reactant: N#Cc1c(-c2ccccc2)c2cc(Cl)ccc2[nH]c1=O
Reactant: O=P(Cl)(Cl)Cl
Solvent: O
Product: N#Cc1c(Cl)nc2ccc(Cl)cc2c1-c1ccccc1
Temperature: 25 °C
Yield: 76.1 %

Procedure:
POCl3 (1.64 g, 1 ml, 10.7 mmol, Eq: 30.1) was added to 6-chloro-2-oxo-4-phenyl-1,2-dihydro-quinoline-3-carbonitrile (100 mg, 356 μmol, Eq: 1.00) and the mixture was refluxed for 1 h. The reaction mixture was then allowed to cool to RT, poured onto cold water and extracted with DCM (3×). The combined organic layers were washed with brine, dried with Na2SO4 and evaporated to dryness. The remaining residue was purified by column chromatography (silica gel, DCM/heptane 1:1) to afford the title compound as white solid (81 mg). MS (ESI): 299.0 (M+H)+.
Reaction SMILES: [C:1]([N:3]=[C:4](SC)[NH:5][C@@H:6]1[C:11]2[CH:12]=[C:13]([C:16]#[N:17])[CH:14]=[CH:15][C:10]=2[O:9][C:8]([CH3:19])([CH3:18])[C@H:7]1[OH:20])#[N:2].[CH3:23][NH2:24]>C(O)C>[C:1]([N:3]=[C:4]([NH:24][CH3:23])[NH:5][C@@H:6]1[C:11]2[CH:12]=[C:13]([C:16]#[N:17])[CH:14]=[CH:15][C:10]=2[O:9][C:8]([CH3:19])([CH3:18])[C@H:7]1[OH:20])#[N:2]
Reactant: CSC(=NC#N)N[C@@H]1c2cc(C#N)ccc2OC(C)(C)[C@H]1O
Reactant: CN
Solvent: CCO
Product: CNC(=NC#N)N[C@@H]1c2cc(C#N)ccc2OC(C)(C)[C@H]1O

Procedure:
The mixture of trans-4-(3-cyano-2-methyl-1-isothioureido)-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.50 g) and 25% aqueous methylamine (10 ml) in ethanol (10 ml) was stirred under reflux for 1 hour and 10 minutes. The solvent was evaporated under reduced pressure. The residue was dissolved in ethyl acetate (30 ml), dried over magnesium sulfate and evaporated in vacuo. The residue was subjected to column chromatography on silica gel (10 g) and eluted with chloroform and then a mixture of chloroform and methanol (20:1). The fractions containing the object compound were combined and concentrated under reduced pressure. The residue was triturated with diisopropyl ether to give trans-4-(2-cyano-3-methylguanidino)-3,4-dihydro-3-hydroxy-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (0.38 g).
Reaction SMILES: CN.C1N=[CH:6][N:5]([C:8]([N:10]2C=N[CH:12]=[CH:11]2)=[O:9])C=1.CCN(C(C)C)C(C)C.NCC[C@@:27]1([C:50]2[CH:55]=[CH:54][C:53]([F:56])=[CH:52][CH:51]=2)[O:32][C:31](=[O:33])[N:30]([C@H:34]([C:36]2[CH:41]=[CH:40][C:39]([C:42]3[CH:47]=[CH:46][C:45]([F:48])=[CH:44][C:43]=3[F:49])=[CH:38][CH:37]=2)[CH3:35])[CH2:29][CH2:28]1>C(Cl)Cl>[F:49][C:43]1[CH:44]=[C:45]([F:48])[CH:46]=[CH:47][C:42]=1[C:39]1[CH:40]=[CH:41][C:36]([C@@H:34]([N:30]2[CH2:29][CH2:28][C@:27]([CH2:12][CH2:11][NH:10][C:8]([NH:5][CH3:6])=[O:9])([C:50]3[CH:51]=[CH:52][C:53]([F:56])=[CH:54][CH:55]=3)[O:32][C:31]2=[O:33])[CH3:35])=[CH:37][CH:38]=1
Reactant: O=C(n1ccnc1)n1ccnc1
Reactant: C[C@@H](c1ccc(-c2ccc(F)cc2F)cc1)N1CC[C@](CCN)(c2ccc(F)cc2)OC1=O
Agent: CN
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Product: CNC(=O)NCC[C@]1(c2ccc(F)cc2)CCN([C@@H](C)c2ccc(-c3ccc(F)cc3F)cc2)C(=O)O1
Temperature: 25 °C
Reaction time: 8 h
Yield: 11.1 %

Procedure:
To a solution of methylamine (11 mg, 0.11 mmol) and CDI (20 mg, 0.13 mmol) in anhydrous CH2Cl2 (3 mL) was added DIEA (130 mg, 1.00 mmol) at 0° C. under nitrogen. The resulting mixture was stirred at ambient temperature for 1 h. (R)-6-(2-aminoethyl)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-1,3-oxazinan-2-one (40 mg, 0.088 mmol) was added to the above mixture, and the mixture was stirred at rt overnight. The mixture was concentrated in vacuo to give a residue, which was purified by preparative HPLC to afford 1-(2-((R)-3-((S)-1-(2′,4′-difluorobiphenyl-4-yl)ethyl)-6-(4-fluorophenyl)-2-oxo-1,3-oxazinan-6-yl)ethyl)-3-methylurea (5 mg, 12%). 1H NMR (CDCl3): 1.56 (m, 3H), 2.10-2.30 (m, 4H), 2.35 (m, 1H), 2.75 (s, 3H), 3.01 (m, 1H), 3.09 (m, 1H), 3.30 (m, 1H), 5.69 (m, 1H), 6.86-6.96 (m, 2H), 7.08 (m, 4H), 7.25 (m, 2H), 7.30 (m, 3H).
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][CH:9]([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:10][CH2:11][CH2:12][OH:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[CH3:27][S:28](Cl)(=[O:30])=[O:29]>ClCCl>[S:28]([O:13][CH2:12][CH2:11][CH2:10][CH:9]([NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[C:14]1[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=1)(=[O:30])(=[O:29])[CH3:27]
Reactant: CS(=O)(=O)Cl
Reactant: CC(C)(C)OC(=O)NC(CCCO)c1ccccc1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)NC(CCCOS(C)(=O)=O)c1ccccc1
Temperature: 0 °C
Reaction time: 0.25 h

Procedure:
To a 0° C. solution of 4-[(t-butoxycarbonyl)-amino]-4-phenylbutanol (133 mg, 0.5 mmol) in dichloromethane (8 mL) was added triethylamine (0.140 mL, 1.0 mmol), followed by methanesulfonylchloride (0.057 mL, 0.75 mmol). The solution was then stirred at 0° C. for 15 minutes before being quenched with an aqueous ammonium chloride solution (2 mL). The aqueous and organic layers were then separated, the aqueous layer extracted twice with dichloromethane, and the combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to afford 4-[(t-butoxycarbonyl)-amino]-4-phenylbutanol mesylate as a yellow oil, which was used immediately in the next reaction without further purification. 1H NMR (CDCl3) δ 1.43 (s, 9H), 1.67-2.00 (m, 4H), 2.95 (s, 3H), 4.18 (t, 2H, J=7.1 Hz), 4.20 (m, 1H), 4.92 (br s, 1H (NH)), 7.21-7.33 (m, 5H).
Reaction SMILES: C(OCCBr)(=O)CCCCCCC.[Br:14][CH2:15][CH2:16][CH2:17][OH:18].[C:19](Cl)(=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34].N1C=CC=CC=1>C1C=CC=CC=1.C(Cl)(Cl)Cl.CO>[C:19]([O:18][CH2:17][CH2:16][CH2:15][Br:14])(=[O:35])[CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH3:34]
Reactant: OCCCBr
Reactant: CCCCCCCCCCCCCCCC(=O)Cl
Agent: CCCCCCCC(=O)OCCBr
Solvent: c1ccccc1
Solvent: CO
Solvent: ClC(Cl)Cl
Product: CCCCCCCCCCCCCCCC(=O)OCCCBr
Yield: 83.9 %

Procedure:
This intermediate was prepared in a manner analogous to that of 2-bromoethyl octanoate from 3-bromo-1-propanol (2.53 g, 18 mmol), hexadecanoyl chloride (6.25 g, 22.5 mmol), and pyridine (4 mL) in benzene (50 mL). Silica gel chromatography using chloroform/methanol (9: 1) yielded 5.7 g pure product. Yield 69%; liquid; 1H NMR (CDCl3) 0.85-0.95 (t, CH3 (CH2)12), 1.20-1.40 (m, CH3 (CH2)12), 1.55-1.70 (m, CH2 CH2 CO), 2.13-2.23 (m, O CH2 CH2 CH2 Br), 2.28-2.38 (t, CH2 CH2 CO), 3.45-3.50 (t, O CH2 CH2 CH2 Br), 4.35-4.40 (t, O CH2 CH2 CH2 Br).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:17](OCC)=[O:18])=[C:10]([C:13]([F:16])([F:15])[F:14])[S:11][CH:12]=2)=[CH:4][CH:3]=1.[H-].[H-].[H-].[H-].[Li+].[Al+3]>O1CCCC1>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[C:9]([CH2:17][OH:18])=[C:10]([C:13]([F:14])([F:15])[F:16])[S:11][CH:12]=2)=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1c(-c2ccc(Cl)cc2)csc1C(F)(F)F
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCc1c(-c2ccc(Cl)cc2)csc1C(F)(F)F
Temperature: 0 °C

Procedure:
Into a 100-mL 3-necked round-bottom flask (1 atm) purged and maintained with an inert atmosphere of nitrogen, was placed ethyl 4-(4-chlorophenyl)-2-(trifluoromethyl)thiophene-3-carboxylate (1.222 g, 3.65 mmol, 1.00 equiv), tetrahydrofuran (5.0 g, 69.34 mmol, 18.99 equiv). This was followed by the addition of a solution of LiAlH4 (278 mg, 7.33 mmol, 2.01 equiv) in tetrahydrofuran (7.0 mL) dropwise with stirring at 0° C. The resulting solution was stirred for 2.0 h at 25° C. The reaction progress was monitored by LCMS/TLC (ethyl acetate/petroleum ether=1:6). The reaction was then quenched by the addition of 10 mL of water and 5 mL of 2N HCl. The resulting solution was extracted with 3×20 mL of ethyl acetate and the organic layers combined and dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was applied onto a silica gel column with ethyl acetate/petroleum ether (1:4). This resulted in 0.9 g (84%) of [4-(4-chlorophenyl)-2-(trifluoromethyl)thiophen-3-yl]methanol as a white solid.
Reaction SMILES: C[O:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([S:11]([NH2:14])(=[O:13])=[O:12])=[N:8][C:7]=2[CH:15]=1.[Cl-].[Al+3].[Cl-].[Cl-]>CCCCCCC>[OH:2][C:3]1[CH:4]=[CH:5][C:6]2[S:10][C:9]([S:11]([NH2:14])(=[O:13])=[O:12])=[N:8][C:7]=2[CH:15]=1
Reactant: COc1ccc2sc(S(N)(=O)=O)nc2c1
Agent: [Al+3]
Agent: [Cl-]
Solvent: CCCCCCC
Product: NS(=O)(=O)c1nc2cc(O)ccc2s1
Temperature: 0 °C
Yield: 58.8 %

Procedure:
A stirred suspension of 5-methoxy-2-benzothiazolesulfonamide (11.8 g, 0.048 mole) and aluminum chloride (28 g, 0.21 mole) in heptane (500 ml) is heated at reflux for 21/2 hours then cooled. The aluminum chloride complex is decomposed by the addition of ice water (400 ml) to give 6.5 g of 5-hydroxy-2-benzothiazolesulfonamide which melts at 224° C. after reprecipitation from dilute sodium hydroxide with dilute hydrochloric acid.
Reaction SMILES: [C:1]([C:8]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:9]=1[C:10](N(C)OC)=[O:11])#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[CH2:22]([Mg]Cl)[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C1COCC1>[C:1]([C:8]1[CH:19]=[C:18]([O:20][CH3:21])[CH:17]=[CH:16][C:9]=1[C:10](=[O:11])[CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1)#[C:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7]
Reactant: Cl[Mg]Cc1ccccc1
Reactant: CCCCCC#Cc1cc(OC)ccc1C(=O)N(C)OC
Solvent: C1CCOC1
Product: CCCCCC#Cc1cc(OC)ccc1C(=O)Cc1ccccc1
Yield: 89 %

Procedure:
2-(1-Heptyn-1-yl)-N-methyl-N,4-bis(methyloxy)benzamide (111) (0.58 g, 2.00 mmol) was treated with benzylmagnesium chloride in THF to give 0.57 g (89%) of the title compound (112) as a light yellow oil. 1H NMR (400 MHz, CDCl3): δ 0.89 (t, J=7.2 Hz, 3H), 1.30-1.50 (m, 4H), 1.60-1.70 (m, 2H), 2.45 (t, J=7.2 Hz, 2H), 3.83 (s, 3H), 4.44 (s, 2H), 6.82 (dd, J1=8.8 Hz, J2=2.8 Hz, 1H), 6.97 (d, J=2.7 Hz, 1H), 7.19-7.26 (m, 3H), 7.27-7.32 (m, 2H), 7.65 (d, J=8.8 Hz, 1H). LCMS (ESI): m/z 321 (M+H)+, m/z 319 (M−H)−.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:24]=[C:25]([O:29][CH3:30])[C:26]=1[O:27][CH3:28])[CH2:6][NH:7][CH2:8][CH2:9][NH:10][CH2:11][C:12]1[CH:17]=[C:16]([O:18][CH3:19])[C:15]([O:20][CH3:21])=[C:14]([O:22][CH3:23])[CH:13]=1.Cl[CH2:32][C:33]1[N:34]=[C:35]([CH3:38])[S:36][CH:37]=1>C(O)C.O.O.C(O)C>[CH3:38][C:35]1[S:36][CH:37]=[C:33]([CH2:32][N:10]([CH2:11][C:12]2[CH:13]=[C:14]([O:22][CH3:23])[C:15]([O:20][CH3:21])=[C:16]([O:18][CH3:19])[CH:17]=2)[CH2:9][CH2:8][N:7]([CH2:32][C:33]2[N:34]=[C:35]([CH3:38])[S:36][CH:37]=2)[CH2:6][C:5]2[CH:24]=[C:25]([O:29][CH3:30])[C:26]([O:27][CH3:28])=[C:3]([O:2][CH3:1])[CH:4]=2)[N:34]=1
Reactant: Cc1nc(CCl)cs1
Reactant: COc1cc(CNCCNCc2cc(OC)c(OC)c(OC)c2)cc(OC)c1OC
Solvent: CCO
Solvent: O
Product: COc1cc(CN(CCN(Cc2cc(OC)c(OC)c(OC)c2)Cc2csc(C)n2)Cc2csc(C)n2)cc(OC)c1OC
Temperature: 45 °C

Procedure:
1.5 g N,N'-bis-(3,4,5-trimethoxybenzyl) ethylenediamine dichlorhydrate were solubilized in 30 ml of a 1:1 ethanol/water mixture. The pH of the solution was brought to 11 using a soda solution. A solution of 1.25 g 4-chloromethyl-2-methylthiazole in solution in 10 ml water were added all at once. The mixture was heated for 5 hours at 45° C., while maintaining the pH at between 10 and 11 by adding a soda solution. After cooling, the ethanol was evaporated under a vacuum and the mixture was acidified to a pH of 1 using concentrated HCl. Extraction was carried out using 3×25 ml dichloromethane, then the organic phase was dried and dry-evaporation effected. The oil obtained was taken up in 10 ml ethanol +0.5 ml concentrated HCl. The resultant precipitate was filtered and washed in ethylic ether. The solid was then recrystallized in 20 ml isopropanol containing 1% water. In this way, 600 mg of a white powder having a melting point of 190° C. was obtained, whose proton NMR spectrum (400 MHZ) and ultimate analysis matched the expected structure (existing as a dichlorhydrate).
Reaction SMILES: Br[CH:2]1[C:8](=O)[C:7]2[CH:10]=[CH:11][CH:12]=[CH:13][C:6]=2[N:5]([C:14](=[O:24])[C:15]2[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=2)[CH2:4][CH2:3]1.[C:25]([NH2:28])(=[S:27])[CH3:26]>C(O)C>[CH3:26][C:25]1[S:27][C:2]2[CH2:3][CH2:4][N:5]([C:14](=[O:24])[C:15]3[CH:20]=[CH:19][C:18]([N+:21]([O-:23])=[O:22])=[CH:17][CH:16]=3)[C:6]3[CH:13]=[CH:12][CH:11]=[CH:10][C:7]=3[C:8]=2[N:28]=1
Reactant: CC(N)=S
Reactant: O=C1c2ccccc2N(C(=O)c2ccc([N+](=O)[O-])cc2)CCC1Br
Solvent: CCO
Product: Cc1nc2c(s1)CCN(C(=O)c1ccc([N+](=O)[O-])cc1)c1ccccc1-2
Yield: 96.7 %

Procedure:
A mixture of 1.19 g of 4-bromo-1,2,3,4-tetrahydro-1-(4-nitrobenzoyl)-5H-1-benzazepin-5-one and 0.230 g of thioacetamide in 4 ml of ethyl alcohol is refluxed under argon for 18 hours. The volatiles are evaporated in vacuo to a residue which is partitioned between CHCl3 and 10% NaHCO3. The organic layer is separated and washed twice with water. The organic layer is separated, dried (MgSO4) and evaporated in vacuo to give 1.08 g of yellow foam which is purified by flash chromatography on silica by elution with 4% ethyl acetate in methylene chloride to give 560 mg of the desired product as pale yellow foam.
Reaction SMILES: [CH2:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1)[CH:2]=[CH2:3].ClC1C=CC=C(C(OO)=[O:18])C=1.ClC1C=C(C=CC=1)C(O)=O>C(Cl)(Cl)Cl>[CH2:1]([C:4]12[O:18][CH:5]1[CH:6]=[CH:7][CH:8]=[CH:9]2)[CH:2]=[CH2:3]
Reactant: C=CCc1ccccc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C(O)c1cccc(Cl)c1
Solvent: ClC(Cl)Cl
Product: C=CCC12C=CC=CC1O2
Reaction time: 55 h
Yield: 68.9 %

Procedure:
21.6 g of allylbenzene was dissolved in 200 ml of chloroform and to the mixture was added dropwise 41.4 g of m-chloroperbenzoic acid dissolved in 1l of chloroform at 0° - 5° C. The resulting mixture was reacted with slow stirring for 55 hours while maintaining the temperature at 0° - 5° C. After the completion of the reaction, m-chlorobenzoic acid crystals were filtered off and the filtrate was washed twice with 5% sodium hydroxide solution and then water. After dried over anhydrous sodium sulfate, the solvent was evaporated to obtain the residue. This was distilled under reduced pressure to give 16.9 g (yield 70.5%) of allylbenzene oxide as colourless oil having a boiling point of 60° C/2 mmHg.
Reaction SMILES: [Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[C:9]([CH:11](OCC)[O:12]CC)[N:8]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[C:6]=2[N:7]=1.Cl.O.CCCCCCC.C(OCC)(=O)C>O1CCOCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:10]=[C:9]([CH:11]=[O:12])[N:8]([CH:18]3[CH2:19][CH2:20][CH2:21][CH2:22]3)[C:6]=2[N:7]=1
Reactant: CCOC(OCC)c1cc2cnc(Cl)nc2n1C1CCCC1
Agent: Cl
Solvent: C1COCCO1
Solvent: O
Solvent: CCCCCCC
Product: O=Cc1cc2cnc(Cl)nc2n1C1CCCC1
Reaction time: 0.17 h
Yield: 82.9 %

Procedure:
A mixture of 2-chloro-7-cyclopentyl-6-diethoxymethyl-7H-pyrrolo[2,3-d]pyrimidine (4.26 g, 13 mmol) in dioxane is added concentrated HCl. After reaction is completed within 10 min, water is added and then extracted with ethyl acetate. Solvent is removed to give a brown color crude product. Column is run using heptane/ethyl acetate (6:4) to give 2-chloro-7-cyclopentyl-7H-pyrrolo[2,3-d]pyrimidine-6-carbaldehyde (2.69 g, 82%). MS (ESI) m/z 350.4 (M+H)+
Reaction SMILES: [C:1]([C:3]1[CH:4]=[CH:5][C:6]([O:12][CH:13]([CH3:15])[CH3:14])=[C:7]([CH:11]=1)[C:8]([OH:10])=O)#[N:2].[C:16]1([C:22]2[N:26]=[C:25]([N:27]3[CH2:32][CH2:31][NH:30][CH2:29][CH2:28]3)[S:24][N:23]=2)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>>[CH:13]([O:12][C:6]1[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:11][C:7]=1[C:8]([N:30]1[CH2:31][CH2:32][N:27]([C:25]2[S:24][N:23]=[C:22]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[N:26]=2)[CH2:28][CH2:29]1)=[O:10])([CH3:15])[CH3:14]
Reactant: c1ccc(-c2nsc(N3CCNCC3)n2)cc1
Reactant: CC(C)Oc1ccc(C#N)cc1C(=O)O
Product: CC(C)Oc1ccc(C#N)cc1C(=O)N1CCN(c2nc(-c3ccccc3)ns2)CC1
Yield: 74 %

Procedure:
Prepared in analogy to example 1 (b) from 5-cyano-2-isopropoxy-benzoic acid (Example A28) and 3-phenyl-5-piperazino-1,2,4-thiadiazole. The crude material was purified by chromatography (SiO2, ethyl acetate/heptane) to yield the title compound as a white solid (yield 74%). MS (m/e): 434.1 (M+H+, 100%).
Reaction SMILES: [CH2:1]([C@H:7]1[C@H:10]([CH2:11][C@H:12](O)[CH2:13][CH2:14]/[CH:15]=C\CCCCCCC)[O:9][C:8]1=[O:25])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[CH:26]([NH:28][C@H:29]([C:34]([OH:36])=[O:35])[CH2:30]C(C)C)=[O:27]>>[CH2:1]([C@@H:7]1[C:8](=[O:25])[O:9][C@@H:10]1[C@@H:11]([O:36][C:34](=[O:35])[C@H:29]([CH3:30])[NH:28][CH:26]=[O:27])[CH2:12][CH2:13][CH:14]=[CH2:15])[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6]
Reactant: CC(C)C[C@H](NC=O)C(=O)O
Reactant: CCCCCCC/C=C\CC[C@@H](O)C[C@@H]1OC(=O)[C@H]1CCCCCC
Product: C=CCC[C@H](OC(=O)[C@H](C)NC=O)[C@H]1OC(=O)[C@H]1CCCCCC

Procedure:
by esterifying (S)-3-hexyl-(S)-4-[(R,Z)-2-hydroxy-5-tridecenyl)-2-oxetanone with N-formyl-L-leucine there was obtained
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[N:5]=[CH:4][C:3]=1[NH:12][CH:13]=O.Cl.[CH2:16]([O:18][NH2:19])[CH3:17]>C(O)(C)C>[CH2:16]([O:18][N:19]1[C:2]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[N:5]=[CH:4][C:3]=2[N:12]=[CH:13]1)[CH3:17]
Reactant: CCON
Reactant: O=CNc1cnc2ccccc2c1Cl
Agent: Cl
Solvent: CC(C)O
Product: CCOn1cnc2cnc3ccccc3c21
Temperature: 25 °C
Reaction time: 0.25 h
Yield: 47.9 %

Procedure:
A solution of 4-chloroquinolin-3-ylformamide (5.0 g, 24 mmol), O-ethylhydroxylamine hydrochloride (2.95 g, 30.2 mmol), and isopropanol (75 mL) was heated at reflux overnight, allowed to cool to room temperature, and concentrated under reduced pressure. The residue was stirred with dichloromethane (150 mL) and saturated aqueous sodium carbonate (50 mL) for 15 minutes. The organic layer was separated and dried over potassium carbonate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 2% methanol in dichloromethane containing 5 mL of aqueous ammonium hydroxide per liter of eluent) to provide 2.45 g of 1-ethoxy-1H-imidazo[4,5-c]quinoline.