Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: FC1C=CC(C2(CC[C:16]3[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][C:17]=34)=[CH:25][C:24]([CH:29]([OH:32])[CH2:30][OH:31])=[CH:23][CH:22]=5)CCCCC2)=CC=1.[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([CH:40]2[CH2:45][CH2:44][CH:43](C3ON=C4C5C(CCC=34)=CC(C=C)=CC=5)[CH2:42][CH2:41]2)=[CH:36][CH:35]=1>>[Cl:33][C:34]1[CH:39]=[CH:38][C:37]([CH:40]2[CH2:45][CH2:44][CH:43]([C:16]3[O:20][N:19]=[C:18]4[C:21]5[C:26]([CH2:27][CH2:28][C:17]=34)=[CH:25][C:24]([CH:29]([OH:32])[CH2:30][OH:31])=[CH:23][CH:22]=5)[CH2:42][CH2:41]2)=[CH:36][CH:35]=1
Reactant: OCC(O)c1ccc2c(c1)CCc1c-2noc1CCC1(c2ccc(F)cc2)CCCCC1
Reactant: C=Cc1ccc2c(c1)CCc1c-2noc1C1CCC(c2ccc(Cl)cc2)CC1
Product: OCC(O)c1ccc2c(c1)CCc1c-2noc1C1CCC(c2ccc(Cl)cc2)CC1

Procedure:
This compound was prepared according to the general procedure described for Preparation 26B employing 3-(4-(4-chlorophenyl)cyclohexyl)-7-vinyl-4,5-dihydronaphtho[1,2-c]isoxazole (Preparation 27B) as the starting material. LC/MS M+1=424.19.
Reaction SMILES: C([Si](C(C)C)(C(C)C)[O:5][C:6]1[CH:14]=[CH:13][CH:12]=[C:8]([C:9]([OH:11])=[O:10])[C:7]=1[NH2:15])(C)C.[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:24]=1[C:25](Cl)=O.C(NC1C=CC2N=C(C3C(F)=CC=CC=3F)OC(=O)C=2C=1)(=O)C.Cl>C1COCC1.C(OCC)(=O)C.C(N(CC)CC)C.C1(C)C=CC=CC=1>[F:22][C:23]1[CH:31]=[CH:30][CH:29]=[C:28]([F:32])[C:24]=1[C:25]1[O:11][C:9](=[O:10])[C:8]2[CH:12]=[CH:13][CH:14]=[C:6]([OH:5])[C:7]=2[N:15]=1
Reactant: O=C(Cl)c1c(F)cccc1F
Reactant: CC(C)[Si](Oc1cccc(C(=O)O)c1N)(C(C)C)C(C)C
Agent: CC(=O)Nc1ccc2nc(-c3c(F)cccc3F)oc(=O)c2c1
Agent: Cl
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Solvent: CCOC(C)=O
Product: O=c1oc(-c2c(F)cccc2F)nc2c(O)cccc12
Temperature: 25 °C
Reaction time: 48 h

Procedure:
3-Triisopropylsilyloxyanthranilic acid (0.8 g), 2,6-difluorobenzoyl chloride (0.71 mL) and triethyl amine/toluene (1/1) (25 mL) were reacted as described under (10). Reaction time 2 days. Extraction between ethyl acetate (100 mL) and HCl (1N,100 mL), followed by separation of the organic layer, drylng over MgSO4, filtering and evaporation gave a crude product which was dissolved in warm THF (20 mL) and precipitated with hexane. The resulting mixture was further purified on a silicagel column using dichloromethane as eluent. The isolated fraction (80 mg) was hydrolysed with 1% HCl in ethanol by stirring for 2 days at RT, and further hydrolysis after addition of HCl (4N, 5 mL) and ethyl acetate (10 mL). The organic layer was separated, evaporated and dried resulting in 2-(2,6-difluoro-phenyl)-8-hydroxy-benzo[d][1,3]oxazin-4-one (32 mg), mp.190-198. LC-MS showed the purity 86% with the corresponding O-triisopropylsilylated product as the impurity.
Reaction SMILES: [Cl:1][C:2]1[CH:30]=[CH:29][C:5]([CH2:6][C:7]2[N:8]=[C:9]([O:25][CH2:26][CH2:27][CH3:28])[C:10]3[N:15]=[C:14]([C:16]4[CH:21]=[C:20]([CH3:22])[C:19]([OH:23])=[C:18]([CH3:24])[CH:17]=4)[O:13][C:11]=3[N:12]=2)=[CH:4][CH:3]=1.[Br:31][CH2:32][CH2:33][CH2:34]Br.C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O>[Br:31][CH2:32][CH2:33][CH2:34][O:23][C:19]1[C:18]([CH3:24])=[CH:17][C:16]([C:14]2[O:13][C:11]3[N:12]=[C:7]([CH2:6][C:5]4[CH:29]=[CH:30][C:2]([Cl:1])=[CH:3][CH:4]=4)[N:8]=[C:9]([O:25][CH2:26][CH2:27][CH3:28])[C:10]=3[N:15]=2)=[CH:21][C:20]=1[CH3:22]
Reactant: CCCOc1nc(Cc2ccc(Cl)cc2)nc2oc(-c3cc(C)c(O)c(C)c3)nc12
Reactant: BrCCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Product: CCCOc1nc(Cc2ccc(Cl)cc2)nc2oc(-c3cc(C)c(OCCCBr)c(C)c3)nc12
Temperature: 60 °C
Yield: 59.6 %

Procedure:
A mixture of 300 mg of 4-[5-(4-chloro-benzyl)-7-propoxy-oxazolo[5,4-d]pyrimidin-2-yl]-2,6-dimethyl-phenol (example 17), 286 mg of 1,3-dibromopropane and 98 mg of potassium carbonate in 10 ml of dimethylformamide was heated to 60° C. for 3 h. After cooling to room temperature, the solids were removed by filtration. The solvent was distilled off in vacuo and the residue was purified by chromatography (method SC1) to yield 230 mg of the title compound.
Reaction SMILES: [CH3:1][C:2]1[NH:3][C:4]2[C:5](=[O:14])[CH2:6][CH2:7][CH2:8][C:9]=2[C:10]=1[C:11]([OH:13])=O.[CH3:15][N:16]([CH3:20])[CH2:17][CH2:18][NH2:19]>>[CH3:15][N:16]([CH3:20])[CH2:17][CH2:18][NH:19][C:11]([C:10]1[C:9]2[CH2:8][CH2:7][CH2:6][C:5](=[O:14])[C:4]=2[NH:3][C:2]=1[CH3:1])=[O:13]
Reactant: Cc1[nH]c2c(c1C(=O)O)CCCC2=O
Reactant: CN(C)CCN
Product: Cc1[nH]c2c(c1C(=O)NCCN(C)C)CCCC2=O
Yield: 79.7 %

Procedure:
Similar procedure as Example 2, 2-methyl-7-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (S4) 0.2 g (1.0 mmol) and N1,N1-dimethylethane-1,2-diamine 0.19 g (2.1 mmol) was reacted to give 0.21 g (80%) of the titled compound as a white solid.
Reaction SMILES: C([Sn](CCCC)(CCCC)[C:6]1[O:7][CH:8]=[CH:9][CH:10]=1)CCC.[ClH:19].Br[C:21]1[CH:22]=[CH:23][C:24]2[N:30]([CH2:31][C:32]3[N:33]=[CH:34][NH:35][CH:36]=3)[CH2:29][CH2:28][N:27]([C:37]([C:39]3[C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[CH:42]=[CH:41][CH:40]=3)=[O:38])[CH2:26][C:25]=2[CH:49]=1>>[ClH:19].[ClH:19].[O:7]1[CH:8]=[CH:9][CH:10]=[C:6]1[C:21]1[CH:22]=[CH:23][C:24]2[N:30]([CH2:31][C:32]3[N:33]=[CH:34][NH:35][CH:36]=3)[CH2:29][CH2:28][N:27]([C:37]([C:39]3[C:48]4[C:43](=[CH:44][CH:45]=[CH:46][CH:47]=4)[CH:42]=[CH:41][CH:40]=3)=[O:38])[CH2:26][C:25]=2[CH:49]=1
Reactant: O=C(c1cccc2ccccc12)N1CCN(Cc2c[nH]cn2)c2ccc(Br)cc2C1
Reactant: CCCC[Sn](CCCC)(CCCC)c1ccco1
Agent: Cl
Product: O=C(c1cccc2ccccc12)N1CCN(Cc2c[nH]cn2)c2ccc(-c3ccco3)cc2C1
Yield: 11 %

Procedure:
Example 38 was prepared as a green solid in 11% yield from Compound A of Example 37 and 2-(tributylstannyl)furan as described for Compound B of Example 37.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[C:5]([C:13]#[N:14])=[C:4](S(C)=O)[N:3]=1.Cl.[NH2:19][CH2:20][CH2:21][NH:22][S:23]([C:26]1[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=1)(=[O:25])=[O:24].C1CCN2C(=NCCC2)CC1>COCCOC>[NH2:1][C:2]1[N:3]=[C:4]([NH:19][CH2:20][CH2:21][NH:22][S:23]([C:26]2[CH:31]=[CH:30][C:29]([Cl:32])=[CH:28][CH:27]=2)(=[O:25])=[O:24])[C:5]([C:13]#[N:14])=[C:6]([C:8]2[O:9][CH:10]=[CH:11][CH:12]=2)[N:7]=1
Reactant: NCCNS(=O)(=O)c1ccc(Cl)cc1
Reactant: CS(=O)c1nc(N)nc(-c2ccco2)c1C#N
Agent: Cl
Solvent: COCCOC
Solvent: C1CCC2=NCCCN2CC1
Product: N#Cc1c(NCCNS(=O)(=O)c2ccc(Cl)cc2)nc(N)nc1-c1ccco1

Procedure:
From 2-amino-4-furan-2-yl-6-methanesulfinyl-pyrimidine-5-carbonitrile, N-(2-aminoethyl)-p-chlorobenzenesulfonamide hydrochloride and DBU in DME. ES-MS m/e (%): 419 (M+H+, 100).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.Br[CH2:10][C:11]([O:13][CH3:14])=[O:12].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[Br:1][C:2]1[CH:3]=[CH:4][C:5](=[O:8])[N:6]([CH2:10][C:11]([O:13][CH3:14])=[O:12])[CH:7]=1
Reactant: O=c1ccc(Br)c[nH]1
Reactant: COC(=O)CBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CS(C)=O
Product: COC(=O)Cn1cc(Br)ccc1=O
Temperature: 60 °C
Reaction time: 4 h

Procedure:
To solution of 5-bromopyridin-2(1H)-one (2.5 g, 14.37 mmol) and methyl 2-bromoacetate (2.418 g, 15.81 mmol) in DMSO (12 mL) was added K2CO3 (2.383 g, 17.24 mmol). The mixture was stirred at 60° C. for 4 hours, filtered, and purified via preparative HPLC, eluting with a gradient of 10-90% ACN (containing 0.035% TFA) in H2O (containing 0.05% TFA) to give the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:17]=[CH:16][C:6]([CH2:7][N:8]2[C:13](=O)[CH2:12][CH2:11][CH2:10][C:9]2=[O:15])=[CH:5][CH:4]=1.CCC(C)[BH-](C(C)CC)C(C)CC.[Li+].CCN(C(C)C)C(C)C.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.CN(C1C=CN=CC=1)C>[CH3:1][O:2][C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[CH:13]=[CH:12][CH2:11][CH2:10][C:9]2=[O:15])=[CH:16][CH:17]=1
Reactant: COc1ccc(CN2C(=O)CCCC2=O)cc1
Agent: CCC(C)[BH-](C(C)CC)C(C)CC
Agent: CN(C)c1ccncc1
Agent: [Li+]
Solvent: CCN(C(C)C)C(C)C
Solvent: Cc1ccccc1
Solvent: O=C(OC(=O)C(F)(F)F)C(F)(F)F
Product: COc1ccc(CN2C=CCCC2=O)cc1
Temperature: -78 °C
Reaction time: 1 h
Yield: 91.6 %

Procedure:
1-(4-methoxybenzyl)piperidine-2,6-dione (8.99 g, 38.5 mmol) was dissolved in Toluene (Volume: 128 ml) and cooled to −78° C. L-Selectride (42.4 ml, 42.4 mmol) was added dropwise and the mixture agitated for 1 h. After 1 h, thick slurry along with precipitate observed. Reaction mixture was briefly pulled outside cooling bath to homogenize the mixture. Then DMAP (0.047 g, 0.385 mmol) was added in one portion and then DIEA (38.4 ml, 220 mmol) was added and then TFAA (6.53 ml, 46.2 mmol) was added. Then the cooling flask was removed and the mixture agitated at room temperature for 2 h and then quenched with water and the product extracted with EtOAc. The combined organic layer was dried (MgSO4), filtered and concentrated in vacuo to afford crude residue which was purified by flash chromatography to afford 7.66 g of the desired product as a yellow syrup. LCMS (m/z): (MH+), 234.2, 0.73 min.
Reaction SMILES: CO.[NH:3]([C:10]1[CH:18]=[C:17]([C:19](O)=[O:20])[C:16]([NH:22][C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:15][C:11]=1[C:12](O)=[O:13])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>[Cl-].C([N+](CCCCCCCCCCCCCCCCCC)(C)C)CCCCCCCCCCCCCCCCC.O>[CH:26]1[CH:27]=[C:28]2[C:19]([C:17]3[C:16]([NH:22][C:23]2=[CH:24][CH:25]=1)=[CH:15][C:11]1[C:12]([C:9]2[C:4]([NH:3][C:10]=1[CH:18]=3)=[CH:5][CH:6]=[CH:7][CH:8]=2)=[O:13])=[O:20]
Reactant: O=C(O)c1cc(Nc2ccccc2)c(C(=O)O)cc1Nc1ccccc1
Agent: CCCCCCCCCCCCCCCCCC[N+](C)(C)CCCCCCCCCCCCCCCCCC
Agent: [Cl-]
Solvent: O
Solvent: CO
Product: O=c1c2ccccc2[nH]c2cc3c(=O)c4ccccc4[nH]c3cc12
Temperature: 100 °C
Reaction time: 0.5 h

Procedure:
225 parts of polyphosphoric acid (P2O5 content 85.5%) are heated to 50° C. 3.75 parts of methanol are then added dropwise in the course of 10 minutes. After stirring for 30 minutes the mixture is raised to 100° C. and is stirred at this temperature for 2 hours. It is then raised to 120° C. On reaching this temperature 50 parts of 2,5-dianilinoterephthalic acid are added with stirring in the course of 1 hour. After the mixture has been stirred at 120° C. for a further hour 1 part of distearyldimethylammonium chloride is added, and the mixture is stirred at 120° C. for a further hour. The melt is then hydrolyzed with 300 parts of ice and 375 parts of water. The crude quinacridone is separated off by filtration and is washed with water until neutral. The water-moist crude quinacridone is suspended in 300 parts of water and 75 parts of 10% strength potassium hydroxide solution are added. The suspension thus obtained is bulked to 750 parts with water and is then boiled with stirring for 7 hours. The suspended particles are then filtered off and washed with water until neutral. The isolated neutral moist quinacridone is suspended in 300 parts of 80% strength isobutanol, the suspension is stirred at 150° C. in a sealed vessel for 5 hours, and the quinacridone is then isolated as described in Example 1. Drying produces 44.5 parts of bluish red pigment of the pure γ-crystal modification. To measure the gloss, a casting was prepared on plastic film and measured, both steps being carried out as described in Example 1. The gloss value is 52.1.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:29])[C:16](=[O:28])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([SH:27])[CH:18]=2)=[C:4]([O:30][CH3:31])[CH:3]=1.I[CH:33]1[CH2:36][O:35][CH2:34]1.CCN(C(C)C)C(C)C.[NH4+].[Cl-]>C(#N)C.CCOC(C)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH3:14])[N:11]=[CH:10][C:9]=2[N:15]([CH3:29])[C:16](=[O:28])[C:17]2[CH:22]=[C:21]([C:23]([F:26])([F:25])[F:24])[CH:20]=[C:19]([S:27][CH:33]3[CH2:36][O:35][CH2:34]3)[CH:18]=2)=[C:4]([O:30][CH3:31])[CH:3]=1
Reactant: IC1COC1
Reactant: COc1cc(F)ccc1-c1cc(C)ncc1N(C)C(=O)c1cc(S)cc(C(F)(F)F)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOC(C)=O
Solvent: CC#N
Solvent: CCN(C(C)C)C(C)C
Product: COc1cc(F)ccc1-c1cc(C)ncc1N(C)C(=O)c1cc(SC2COC2)cc(C(F)(F)F)c1

Procedure:
To a solution of N-(4-(4-fluoro-2-methoxyphenyl)-6-methylpyridin-3-yl)-3-mercapto-N-methyl-5-(trifluoromethyl)benzamide (0.093 g, 206 μmol) in acetonitrile (2 mL) were added 3-iodooxetane (57.0 mg, 310 μmol) and DIPEA (66.7 mg, 90.1 μL, 516 μmol) and the clear, light yellow solution was heated under reflux for 2.5 hours. The reaction mixture was poured on saturated aqueous NH4Cl solution and EtOAc and the layers were separated. The aqueous layer was extracted twice with EtOAc. The organic layers were dried over MgSO4, filtered, treated with silica gel and evaporated. The compound was purified by silica gel chromatography on a 10 g column using an MPLC system eluting with a gradient of n-heptane:EtOAc (100:0 to 0:100). Colorless foam (0.05 g; 47%). MS (ESI): m/z=507.14 [M+H]+.
Reaction SMILES: CS(O[CH2:6][CH2:7][NH:8][C:9]1[CH:10]=[CH:11][C:12]2[N:13]([CH:15]=[C:16]([C:18]([CH3:26])([CH3:25])[C:19]([O:21]C(C)C)=[O:20])[N:17]=2)[N:14]=1)(=O)=O.[C:27]1([CH:33]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[O:34][CH:35]2[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]2)[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.[I-].[K+].C(=O)([O-])[O-].[K+].[K+].[Cl-].[Na+]>CN(C)C=O>[C:41]1([CH:33]([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[O:34][CH:35]2[CH2:40][CH2:39][N:38]([CH2:6][CH2:7][NH:8][C:9]3[CH:10]=[CH:11][C:12]4[N:13]([CH:15]=[C:16]([C:18]([CH3:25])([CH3:26])[C:19]([OH:21])=[O:20])[N:17]=4)[N:14]=3)[CH2:37][CH2:36]2)[CH:42]=[CH:43][CH:44]=[CH:45][CH:46]=1
Reactant: CC(C)OC(=O)C(C)(C)c1cn2nc(NCCOS(C)(=O)=O)ccc2n1
Reactant: c1ccc(C(OC2CCNCC2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [I-]
Solvent: CN(C)C=O
Product: CC(C)(C(=O)O)c1cn2nc(NCCN3CCC(OC(c4ccccc4)c4ccccc4)CC3)ccc2n1
Temperature: 60 °C
Reaction time: 2 h
Yield: 37.8 %

Procedure:
1.13 g of isopropyl 2-[6-[2-(methanesulfonyloxy) ethylamino]imidazo[1,2-b]pyridazin-2-yl]-2-methylpropionate was dissolved in 15 ml of N,N-dimethylformamide; 943 mg of 4-(diphenylmethoxy)piperidine, 586 mg of potassium iodide and 488 mg of potassium carbonate were added, followed by stirring at 60° C. for 2 hours. Ice water was added; the mixture was saturated with sodium chloride and extracted with ethyl acetate; the extract was washed with saturated saline and dried with magnesium sulfate. The dry product was concentrated under reduced pressure; the residue was subjected to silica gel column chromatography and eluted with ethyl acetate:methanol (10:1). The desired fraction was collected, concentrated under reduced pressure and dried to yield 571 mg of the title compound.
Reaction SMILES: [H-].[Na+].[CH:3]([C:6]1[N:10]=[C:9]([N:11]2[CH2:16][CH2:15][CH:14]([C@H:17]3[CH2:19][C@H:18]3[CH2:20][OH:21])[CH2:13][CH2:12]2)[O:8][N:7]=1)([CH3:5])[CH3:4].[Br:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29]Br)=[C:25]([F:31])[CH:24]=1>CN(C=O)C>[Br:22][C:23]1[CH:28]=[CH:27][C:26]([CH2:29][O:21][CH2:20][C@@H:18]2[CH2:19][C@@H:17]2[CH:14]2[CH2:15][CH2:16][N:11]([C:9]3[O:8][N:7]=[C:6]([CH:3]([CH3:5])[CH3:4])[N:10]=3)[CH2:12][CH2:13]2)=[C:25]([F:31])[CH:24]=1
Reactant: CC(C)c1noc(N2CCC([C@H]3C[C@H]3CO)CC2)n1
Reactant: Fc1cc(Br)ccc1CBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)c1noc(N2CCC([C@H]3C[C@H]3COCc3ccc(Br)cc3F)CC2)n1
Temperature: 0 °C
Reaction time: 1 h
Yield: 88.7 %

Procedure:
Sodium hydride (203 mg, 5.09 mmol) was added to a stirring solution of ((1R,2R)-2-(1-(3-isopropyl-1,2,4-oxadiazol-5-yl)piperidin-4-yl)cyclopropyl)methanol (Step A product, 900 mg, 3.39 mmol) in DMF (9 mL) that had been cooled to 0° C. in an ice bath and placed under an inert atmosphere. 10 min later 4-bromo-1-(bromomethyl)-2-fluorobenzene (1 g, 3.73 mmol) was introduced to the mixture. The ice bath was removed and the reaction warmed to rt. The reaction was aged for 1 hr then diluted with EtOAc (20 mL) and neutralized by the slow addition of saturated aqueous ammonium chloride solution (20 mL). The layers were cut and the aqueous phase extracted with EtOAc (20 mL×2). The combined organic layers were dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was loaded onto a silica column (KP-Sil 50 g SNAP column, Biotage system) eluting with a range of 0-45% EtOAc/Hex over 12 CV to give the desired compound (1.36 g, 89%). LC/MS (m/z): 452 (M+H)+.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]#[C:9][C:10]2[CH:30]=[CH:29][C:13]([CH2:14][NH:15][C:16]3[CH:28]=[CH:27][C:19]4[O:20][C:21]([CH3:26])([CH3:25])[O:22][C:23](=[O:24])[C:18]=4[CH:17]=3)=[CH:12][CH:11]=2)=[CH:4][CH:3]=1.[CH:31]1([CH2:36][CH2:37][C:38](Cl)=[O:39])[CH2:35][CH2:34][CH2:33][CH2:32]1>>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]#[C:9][C:10]2[CH:30]=[CH:29][C:13]([CH2:14][N:15]([C:16]3[CH:28]=[CH:27][C:19]4[O:20][C:21]([CH3:26])([CH3:25])[O:22][C:23](=[O:24])[C:18]=4[CH:17]=3)[C:38](=[O:39])[CH2:37][CH2:36][CH:31]3[CH2:35][CH2:34][CH2:33][CH2:32]3)=[CH:12][CH:11]=2)=[CH:6][CH:7]=1
Reactant: O=C(Cl)CCC1CCCC1
Reactant: CC1(C)OC(=O)c2cc(NCc3ccc(C#Cc4ccc(Cl)cc4)cc3)ccc2O1
Product: CC1(C)OC(=O)c2cc(N(Cc3ccc(C#Cc4ccc(Cl)cc4)cc3)C(=O)CCC3CCCC3)ccc2O1

Procedure:
The titled compound was prepared following the procedure B using 6-({4-[(4-chlorophenyl)ethynyl]benzyl}amino)-2,2-dimethyl-4H-1,3-benzodioxin-4-one and 3-cyclopentylpropanoyl chloride as a white foam (80%). 1H NMR (CDCl3, 300 MHz) δ 7.67 (m, 1H), 7.42 (m, 4H), 7.31 (m, 2H), 7.17 (d, J=7.9 Hz, 2H), 7.06 (m, 1H), 6.89 (d, J=8.7 Hz, 1H), 4.86 (s, 2H), 2.06 (m, 2H), 1.73 (s, 6H), 1.66-1.39 (m, 9H), 0.95 (m, 2H). M+ (ESI): 542.1. HPLC, Rt: 5.83 min (Purity: 97.3%).
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]2[CH:7]([N:13]=[N+]=[N-])[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1.[H][H]>[Pd]>[CH3:1][O:2][C:3]1[CH:4]=[N:5][C:6]2[CH:7]([NH2:13])[CH2:8][CH2:9][CH2:10][C:11]=2[CH:12]=1
Reactant: COc1cnc2c(c1)CCCC2N=[N+]=[N-]
Reactant: [H][H]
Agent: [Pd]
Product: COc1cnc2c(c1)CCCC2N
Yield: 98.2 %

Procedure:
To a solution of (3-methoxy-5,6,7,8-tetrahydroquinolin-8-yl)-azide (0.33 g, 1.6 mmol) in MEOH (16 mL) was added palladium on activated carbon, (10%, 50 mg) and the reaction mixture stirred under 1 atmosphere of hydrogen for 4 h. The mixture was filtered through celite, the cake washed with methanol and the solvent from the eluent removed in vacuo to give crude (3-methoxy-5,6,7,8-tetrahydroquinolin-8-yl)-amine as a yellow oil (0.28 g, 96%). 1H NMR (CDCl3) δ1.75 (m, 2H), 1.97 (m, 1H), 2.17 (m, 1H), 2.77 (m, 2H), 3.81 (s, 3H), 3.98 (t, 1H, J=4.5 Hz), 6.88 (d, 1H, J=1.5 Hz), 8.12 (d, 1H, J=1.5 Hz).
Reaction SMILES: C[N:2]([CH:4]=[C:5]([N:11]1[CH:15]=[C:14]([C:16]#[N:17])[N:13]=[CH:12]1)[C:6]([O:8]CC)=O)C.[NH:18]([C:20]1[N:25]=[CH:24][N:23]=[C:22]([N:26]2[CH2:32][CH2:31][CH2:30][O:29][CH2:28][CH2:27]2)[CH:21]=1)N.FC(F)(F)C(O)=O>O>[O:29]1[CH2:30][CH2:31][CH2:32][N:26]([C:22]2[N:23]=[CH:24][N:25]=[C:20]([N:18]3[C:6](=[O:8])[C:5]([N:11]4[CH:15]=[C:14]([C:16]#[N:17])[N:13]=[CH:12]4)=[CH:4][NH:2]3)[CH:21]=2)[CH2:27][CH2:28]1
Reactant: CCOC(=O)C(=CN(C)C)n1cnc(C#N)c1
Reactant: NNc1cc(N2CCCOCC2)ncn1
Solvent: O
Solvent: O=C(O)C(F)(F)F
Product: N#Cc1cn(-c2c[nH]n(-c3cc(N4CCCOCC4)ncn3)c2=O)cn1
Temperature: 100 °C
Reaction time: 16 h

Procedure:
A mixture of 200 mg (0.9 mmol) of the compound from Example 6A, 178 mg (0.9 mmol) of the compound from Example 14A and 33 μl (49 mg, 0.4 mmol) of trifluoroacetic acid in 3 ml of water is stirred at 100° C. for 16 h. The precipitated solid is filtered off and washed first with water and then with diethyl ether. The product is dried under reduced pressure. Yield: 120 mg (40% of theory)
Reaction SMILES: [OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=O)=[CH:4][CH:3]=1.[NH2:12][C@H:13](CO)[CH:14]([CH3:16])[CH3:15]>ClC1C=CC=CC=1>[CH:14]([C@H:13]1[CH2:9][O:8][C:6]([C:5]2[CH:10]=[CH:11][C:2]([OH:1])=[CH:3][CH:4]=2)=[N:12]1)([CH3:16])[CH3:15]
Reactant: CC(C)[C@H](N)CO
Reactant: COC(=O)c1ccc(O)cc1
Solvent: Clc1ccccc1
Product: CC(C)[C@H]1COC(c2ccc(O)cc2)=N1
Yield: 58 %

Procedure:
Under an argon atmosphere, a mixture of methyl 4-hydroxybenzoate (1.5 mmol), (L)-valinol (1.8 mmol), Zn4(OCOCF3)6O (0.15 mmol) and chlorobenzene (2.5 mL) was heated under reflux for 12 hours. From the resulting solution, the solvent was removed using an evaporator, and the residues were purified by silica gel column chromatography to give (S)-4-isopropyl-2-(4-hydroxyphenyl)-1,3-oxazoline in 58% yield. The compound was identified by comparison with physical property data of the known compound.
Reaction SMILES: [C:1]1([C:7]([C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[S:8][CH2:9][CH2:10][CH2:11][C:12](C(O)=O)([C:18]([OH:20])=[O:19])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1>CS(C)=O>[C:30]1([C:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[S:8][CH2:9][CH2:10][CH2:11][CH:12]([C:18]([OH:20])=[O:19])[CH2:13][CH2:14][C:15]([OH:17])=[O:16])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1
Reactant: O=C(O)CCC(CCCSC(c1ccccc1)(c1ccccc1)c1ccccc1)(C(=O)O)C(=O)O
Solvent: CS(C)=O
Product: O=C(O)CCC(CCCSC(c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)O
Temperature: 100 °C
Reaction time: 1 h

Procedure:
2.56 mmol of 6-[(triphenylmethyl)thio]-1,3,3,-hexanetricarboxylic acid (III) (1.36 g) was dissolved in 5 ml of dimethylsulfoxide and the solution was ad heated to 100° C. for 1 hour, evaporated to dryness, dissolved in water and precipitated by addition of 1 M sulfuric acid. The precipitated oil solidified after 1 hour treatment in an ultrasound bath. The solid was filtered off, washed with water and dried in a dessicator. Yield 1.1 g of 6-[(triphenylmethyl)thio]-1,3-hexanedicarboxylic acid (IV) (89% two steps from II), 13C-NMR (MeOH) δ27.9, 28.6, 33.0 (two carbons), 33.1, 45.9, 68.1, 128.1, 129.2, 131.2, 146.8, 177.1, 179.4.
Reaction SMILES: C1(N2CCN3C(CC4(C5C=CC=CC=5)CCCC4)=NC(=O)C(O)=C3C2=O)CC1.C([O:36][C:37]1[C:42](=[O:43])[N:41]=[C:40]([CH2:44][C:45]2([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[CH2:49][CH2:48][CH2:47][CH2:46]2)[N:39]2[CH2:56][CH2:57][N:58]([CH:61]3[CH2:65][CH2:64][CH2:63][CH2:62]3)[C:59](=[O:60])[C:38]=12)C1C=CC=CC=1>>[CH:61]1([N:58]2[CH2:57][CH2:56][N:39]3[C:40]([CH2:44][C:45]4([C:50]5[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=5)[CH2:46][CH2:47][CH2:48][CH2:49]4)=[N:41][C:42](=[O:43])[C:37]([OH:36])=[C:38]3[C:59]2=[O:60])[CH2:62][CH2:63][CH2:64][CH2:65]1
Reactant: O=C1c2c(OCc3ccccc3)c(=O)nc(CC3(c4ccccc4)CCCC3)n2CCN1C1CCCC1
Agent: O=C1c2c(O)c(=O)nc(CC3(c4ccccc4)CCCC3)n2CCN1C1CC1
Product: O=C1c2c(O)c(=O)nc(CC3(c4ccccc4)CCCC3)n2CCN1C1CCCC1
Yield: 24.5 %

Procedure:
This compound was prepared following the same method as described for 2-cyclopropyl-9-hydroxy-6-(1-phenyl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (287) from 9-benzyloxy-2-cyclopentyl-6-(1-phenyl-cyclopentylmethyl)-3,4-dihydro-2H-pyrazino[1,2-c]pyrimidine-1,8-dione (290) (80 mg, 0.16 mmol). The product was obtained as a white solid (16 mg, 24.42%).
Reaction SMILES: [F:1][C:2]1[CH:15]=[N:14][C:5]2[N:6]=[CH:7][C:8](=[O:13])[N:9]([CH2:10][CH:11]=C)[C:4]=2[CH:3]=1.I([O-])(=O)(=O)=[O:17].[Na+]>O1CCOCC1.O.[Os](=O)(=O)(=O)=O>[F:1][C:2]1[CH:15]=[N:14][C:5]2[N:6]=[CH:7][C:8](=[O:13])[N:9]([CH2:10][CH:11]=[O:17])[C:4]=2[CH:3]=1
Reactant: [O-][I+3]([O-])([O-])[O-]
Reactant: C=CCn1c(=O)cnc2ncc(F)cc21
Agent: O=[Os](=O)(=O)=O
Agent: [Na+]
Solvent: O
Solvent: C1COCCO1
Product: O=CCn1c(=O)cnc2ncc(F)cc21
Temperature: 25 °C
Reaction time: 2 h

Procedure:
7-Fluoro-1-(2-propen-1-yl)pyrido[2,3-b]pyrazin-2(1H)-one (163 mg, 0.795 mmol) was dissolved in 1,4-dioxane (5 ml) and water (5 ml). Sodium periodate (426 mg, 1.99 mmol) was added, followed by osmium tetroxide (0.17 ml of 4% aqueous solution). The mixture stirred at rt for 2 h, and then treated with water (20 ml) and extracted with 20% MeOH/DCM (3×100 ml). The organic extracts were combined, dried over anhydrous magnesium sulphate, filtered and evaporated to give (7-fluoro-2-oxopyrido[2,3-b]pyrazin-1(2H)-yl)acetaldehyde (existing mostly as the methyl hemiacetal) as an impure brown oil (193 mg, 117%).