Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9](O)=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3].O=S(Cl)[Cl:16].C1(C)C=CC=CC=1>C(Cl)Cl>[CH3:1][S:2]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([Cl:16])=[O:10])=[CH:7][CH:6]=1)(=[O:4])=[O:3]
Reactant: O=S(Cl)Cl
Reactant: CS(=O)(=O)c1ccc(C(=O)O)cc1
Solvent: Cc1ccccc1
Solvent: ClCCl
Product: CS(=O)(=O)c1ccc(C(=O)Cl)cc1
Temperature: 60 °C
Reaction time: 20 h

Procedure:
To a stirred solution of 4-methylsulphonylbenzoic acid (100 mg, 0.48 mmol) in DCM (2 mL) was added SOCl2 (52 μL, 0.73 mmol) and toluene (2 mL) and the resulting reaction was stirred at 60° C. for 20 hours. A further charge of SOCl2 (100 μL, 1.45 mmol) was added and the reaction was heated at 80° C. for a further 24 hours. Volatiles were removed at reduced pressure and the crude product used in subsequent steps without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[N:8]=[C:9]=[O:10].[CH3:11][CH:12]([CH3:35])[CH:13]([NH:18][C:19]([C:21]1[S:22][C:23]([C:26]2[CH:31]=[CH:30][C:29]([N+:32]([O-])=O)=[CH:28][CH:27]=2)=[CH:24][N:25]=1)=[O:20])[C:14]([O:16][CH3:17])=[O:15]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH:8][C:9](=[O:10])[NH:32][C:29]1[CH:30]=[CH:31][C:26]([C:23]2[S:22][C:21]([C:19]([NH:18][CH:13]([CH:12]([CH3:35])[CH3:11])[C:14]([O:16][CH3:17])=[O:15])=[O:20])=[N:25][CH:24]=2)=[CH:27][CH:28]=1
Reactant: COC(=O)C(NC(=O)c1ncc(-c2ccc([N+](=O)[O-])cc2)s1)C(C)C
Reactant: O=C=Nc1ccccc1Cl
Product: COC(=O)C(NC(=O)c1ncc(-c2ccc(NC(=O)Nc3ccccc3Cl)cc2)s1)C(C)C
Yield: 87 %

Procedure:
The title compound was synthesized analogous to Example 9, using 1-chloro-2-isocyanatobenzene and intermediate 2. Yield: 87%; 1HNMR (DMSO-d6, 300 MHz): δ 9.67 (s, 1H), 8.74 (d, 1H), 8.38 (s, 1H), 8.36 (s, 1H), 8.15 (dd, 1H), 7.75 (d, 2H), 7.6 (d, 2H), 7.49 (dd, 1H), 7.32 (m, 1H), 7.06 (m, 1H), 4.33, (m, 1H), 3.68 (s, 3H), 2.26 (m, 1H), 0.95 (d, 6H); MS (ES+): m/z 487 (M+1).
Reaction SMILES: [C:1]([O:5][C:6](=[O:27])[N:7]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH2:25][OH:26])[CH:19]=1)[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[OH:16])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].[CH3:30][O:31][CH2:32]Cl>CN(C)C=O>[C:1]([O:5][C:6](=[O:27])[N:7]([CH2:17][C:18]1[CH:23]=[CH:22][CH:21]=[C:20]([CH2:24][CH2:25][OH:26])[CH:19]=1)[CH2:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[O:16][CH2:30][O:31][CH3:32])([CH3:3])([CH3:2])[CH3:4]
Reactant: CC(C)(C)OC(=O)N(CCc1ccccc1O)Cc1cccc(CCO)c1
Reactant: COCCl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: COCOc1ccccc1CCN(Cc1cccc(CCO)c1)C(=O)OC(C)(C)C
Reaction time: 0.17 h
Yield: 79.9 %

Procedure:
A solution of [3-(2-hydroxy-ethyl)-benzyl]-[2-(2-hydroxy-phenyl)-ethyl]-carbamic acid tert-butyl ester (123 mg) in anhydrous N,N-dimethylformamide (2 mL) was treated with sodium hydride (14 mg of 60% grade reagent) and the mixture stirred under nitrogen for 10 minutes. A solution of chloromethyl methyl ether (29 mg) in anhydrous N,N-dimethylformamide (0.5 mL) was added dropwise followed by stirring at room temperature for 30 minutes. The reaction mixture was partitioned between ethyl acetate and saturated aqueous brine, the organic layer was separated, dried and the solvent evaporated under reduced pressure to yield the sub-titled compound (110 mg).
Reaction SMILES: [CH3:1][C:2]([C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)=[CH:6][C:5]=1[OH:18])=[O:3].C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[C:27]([C:29]([CH3:36])([CH3:35])[CH2:30][CH2:31][CH2:32][CH2:33]Br)#[N:28]>CN(C)C=O.O>[CH2:11]([O:10][C:7]1[CH:8]=[CH:9][C:4]([C:2]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:2][CH:1]=2)=[O:3])=[C:5]([O:18][CH2:33][CH2:32][CH2:31][CH2:30][C:29]([CH3:36])([C:27]#[N:28])[CH3:35])[CH:6]=1)[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: CC(=O)c1ccc(OCc2ccccc2)cc1O
Reactant: CC(C)(C#N)CCCCBr
Agent: O=C([O-])[O-]
Agent: [I-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: CC(C)(C#N)CCCCOc1cc(OCc2ccccc2)ccc1C(=O)c1ccccc1
Yield: 111 %

Procedure:
A solution of 4-benzyloxy-2-hydroxyacetophenone (2.45 g), potassium carbonate (3.25 g), potassium iodide (0.42 g), and 5-cyano-5-methyl-1-bromohexane (2.6 g) in dimethylformamide (40 mL) was heated at 90° C. for 22 hours under nitrogen. The slurry was cooled, poured into water (150 mL) and extracted with ethyl acetate. The combined extracts were washed with water, dried (MgSO4), filtered, and concentrated under reduced pressure to an orange oil. This was purified by flash chromatography (ethyl acetate:hexane) to afford the product (2.4 g) as a clear oil. NMR(CDCl3): 1.37, s (6H); 1.64, m (4H); 1.89, m (2H); 2.58, s (3H); 4.03, t (3H); 5.09, s (2H); 6.50, s (1H); 6.58, d (1H); 7.37, m (5 H); 7.81, d (1H). Mass Spec (GC-MS) m/z=365 (M).
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([N+:12]([O-:14])=[O:13])[CH:10]=2)[N:5]=[CH:4][N:3]=1.[NH2:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][CH:20]=[CH:19]2>>[N+:12]([C:9]1[CH:10]=[C:11]2[C:6](=[CH:7][CH:8]=1)[N:5]=[CH:4][N:3]=[C:2]2[NH:15][C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[N:22]=[CH:21][CH:20]=[CH:19]2)([O-:14])=[O:13]
Reactant: Nc1ccc2ncccc2c1
Reactant: O=[N+]([O-])c1ccc2ncnc(Cl)c2c1
Product: O=[N+]([O-])c1ccc2ncnc(Nc3ccc4ncccc4c3)c2c1
Yield: 86 %

Procedure:
Using an analogous procedure to that described in Example 1, 4-chloro-6-nitroquinazoline was reacted with 6-aminoquinoline to give 6-nitro-4-(6-quinolylamino)quinazoline in 86% yield, m.p. >300° C.;
Reaction SMILES: [F:1][C:2]([F:48])([F:47])[S:3](OC1C(C)(C)[C@H]2[C@](C)(CC=1)[C@@H]1[C@](C)([C@@]3(C)[C@H](CC1)[C@H]1[C@H](C(C)=C)CC[C@]1(NCCN1CCS(=O)(=O)CC1)CC3)CC2)(=[O:5])=[O:4].[O:49]=[C:50]1[CH2:54][CH2:53][CH:52]([CH2:55][C:56]([O:58][CH3:59])=[O:57])[CH2:51]1>>[F:1][C:2]([F:48])([F:47])[S:3]([O:49][C:50]1[CH2:51][CH:52]([CH2:55][C:56]([O:58][CH3:59])=[O:57])[CH2:53][CH:54]=1)(=[O:5])=[O:4]
Reactant: C=C(C)[C@@H]1CC[C@]2(NCCN3CCS(=O)(=O)CC3)CC[C@]3(C)[C@H](CC[C@@H]4[C@@]5(C)CC=C(OS(=O)(=O)C(F)(F)F)C(C)(C)[C@@H]5CC[C@]43C)[C@@H]12
Reactant: COC(=O)CC1CCC(=O)C1
Product: COC(=O)CC1CC=C(OS(=O)(=O)C(F)(F)F)C1
Yield: 50.1 %

Procedure:
The title compound was prepared following the procedure described in method 2 for the preparation of intermediate 1, Step 6, using methyl 2-(3-oxocyclopentyl)acetate as the reactant. (50.1% yield). 1H NMR (400 MHz, CHLOROFORM-d) δ 5.66 (q, J=2.1 Hz, 1H), 3.73 (br. s., 3H), 3.29-3.13 (m, 1H), 2.95-2.78 (m, 1H), 2.67-2.57 (m, 2H), 2.49-2.40 (m, 1H), 2.40-2.28 (m, 1H), 1.77-1.63 (m, 1H). 19F NMR (376 MHz, CHLOROFORM-d) δ −73.53 (s, 3F).
Reaction SMILES: [CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[C:8]([CH3:13])=[N:9][CH:10]=[CH:11][CH:12]=1)[CH3:2].[Se](=O)=[O:15].C(OCC)(=O)C>O1CCOCC1>[CH2:1]([O:3][CH2:4][CH2:5][O:6][C:7]1[C:8]([CH:13]=[O:15])=[N:9][CH:10]=[CH:11][CH:12]=1)[CH3:2]
Reactant: CCOCCOc1cccnc1C
Reactant: O=[Se]=O
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Product: CCOCCOc1cccnc1C=O
Temperature: 75 °C
Yield: 38.6 %

Procedure:
A mixture of 3-(2-ethoxyethoxy)-2-methylpyridine (0.506 g, 2.79 mmol) and selenium dioxide (0.31 g, 2.79 mmol) in 1,4-dioxane (10 mL) was heated at 75° C. overnight. After cooling to r.t., the mixture was filtered and the solids were washed with ethyl acetate. The solvent was removed in vacuo. The reaction was not complete and the solid was dissolved in 1,4 dioxane (15 mL) and selenium dioxide (0.31 g, 2.79 mmol) was added. The mixture was heated at 110° C. overnight. Ethyl acetate (10 mL) was added and the mixture was filtered. The black solid was washed with ethyl acetate and the filtrate was evaporated in vacuo. The crude product was purified by flash column chromatography (heptane/ethyl acetate gradient; 0 to 100% ethyl acetate), obtaining 0.21 g (39%) of the title compound.
Reaction SMILES: Br[CH2:2][CH:3]1[O:8][C:7]2[CH:9]=[C:10]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:11]=[CH:12][C:6]=2[CH2:5][O:4]1.[CH3:17][O:18][CH2:19][CH2:20][NH2:21]>CCO>[CH3:17][O:18][CH2:19][CH2:20][NH:21][CH2:2][CH:3]1[O:8][C:7]2[CH:9]=[C:10]([S:13]([CH3:16])(=[O:15])=[O:14])[CH:11]=[CH:12][C:6]=2[CH2:5][O:4]1
Reactant: CS(=O)(=O)c1ccc2c(c1)OC(CBr)OC2
Reactant: COCCN
Solvent: CCO
Product: COCCNCC1OCc2ccc(S(C)(=O)=O)cc2O1

Procedure:
Preparation according to Example 22 using 2-(bromomethyl)-7-(methylsulfonyl)-4H-1,3-benzodioxine (30 mg, 0.10 mmol), 2-methyoxyethanamine (0.50 ml, 5.8 mmol) and EtOH (1.0 ml). MS m/z (rel. intensity, 70 eV) 301 (M+, 1), 123 (13), 88 (bp), 72 (25), 56 (13).
Reaction SMILES: [CH2:1]([C:4]1([OH:17])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].C[Si](C)(C)[C:20]([F:23])(F)[F:21].C1COCC1>C(Cl)Cl>[F:21][C:20]1([F:23])[CH2:3][CH:2]1[CH2:1][C:4]1([OH:17])[CH2:9][CH2:8][N:7]([C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[CH2:6][CH2:5]1
Reactant: C=CCC1(O)CCN(C(=O)OC(C)(C)C)CC1
Reactant: C[Si](C)(C)C(F)(F)F
Solvent: ClCCl
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(O)(CC2CC2(F)F)CC1
Temperature: 80 °C
Reaction time: 8 h

Procedure:
To a sealed tube was added tert-butyl 4-allyl-4-hydroxypiperidine-1-carboxylate 11B (280 mg, 1.16 mmol), Nat (112 mg, 0.74 mmol), trimethyl(trifluoromethyl)silane (0.6 mL) and THF (10 mL). The tube was sealed, and then the mixture was stirred at 80° C. overnight. The resulting mixture was diluted with DCM, filtered, and the filtrate was concentrated in vacuo to give the crude product 11C which was used for next step without further purification. LC-MS: m/z 292.3 (M+H)+
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][NH2:9])[CH:3]=1.[CH:10](O)=O>>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[CH:10]=[N:9][N:8]=[C:4]2[CH:3]=1
Reactant: NNc1cc(Br)ccn1
Reactant: O=CO
Product: Brc1ccn2cnnc2c1
Temperature: 25 °C

Procedure:
A solution of (4-bromo-pyridin-2-yl)-hydrazine (0.50 g) in formic acid (0.50 mL) is stirred at reflux temperature overnight. After cooling to room temperature, the solution was concentrated under reduced pressure. Water was added to the residue and the resulting mixture was extracted with ethyl acetate. The combined organic extracts were washed with brine, dried (MgSO4), and concentrated to give the title compound.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[NH:7][C:8](=[O:13])[C:9]([CH3:12])([CH3:11])[CH3:10].CCCCCC.[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]=[O:26])=[CH:23][CH:22]=1.[Cl-].[NH4+]>O1CCCC1>[F:20][C:21]1[CH:28]=[CH:27][C:24]([CH:25]([OH:26])[C:3]2[C:2]([NH:7][C:8](=[O:13])[C:9]([CH3:10])([CH3:12])[CH3:11])=[N:1][CH:6]=[CH:5][CH:4]=2)=[CH:23][CH:22]=1
Reactant: O=Cc1ccc(F)cc1
Reactant: CC(C)(C)C(=O)Nc1ccccn1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: CCCCCC
Product: CC(C)(C)C(=O)Nc1ncccc1C(O)c1ccc(F)cc1
Temperature: 0 °C
Reaction time: 2 h

Procedure:
To a solution of N-(pyridin-2-yl)pivalamide (1.84 g, 10 mmol) in tetrahydrofurane (100 mL) was added at −78° C. under an atmosphere of nitrogen 1.6 M butyl lithium in hexane (13.1 mL, 21 mmol). The reaction is slighly exothermic and a yellow color appears. The reaction is warmed to 0° C. within 15 minutes and stirred at 0° C. for 2 hours. A white suspension is formed. The reaction is cooled to −78° C. and 4-fluorobenzaldehyde (1.52 g, 1.29 mL, 12.0 mmol) was added in tetrahydrofurane (6.55 mL). The reaction was warmed to room temperature over night to yield an orange suspension. Saturated aqueous ammonium chloride solution was added and the reaction was extracted twice with ethyl acetate and once with methylene chloride. The combined organic layers were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and the solvent was evaporated under reduced pressure. The title compound was obtained as a yellow viscous oil (1.058 g, 35%) after purification by column chromatography on silica gel using a gradient from CH2Cl2 to CH2Cl2/MeOH 19:1 (v/v) as eluent. MS ISP (m/e): 303.1 (100) [(M+H)+].
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:15][C:14]3[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:13]=3[CH:12]=2)=[CH:7][CH:6]=1.[C:22](Cl)(=[O:31])[C:23]1[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=1.B(Cl)(Cl)Cl>CO.C(Cl)Cl>[CH3:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([C:11]2[S:15][C:14]3[CH:16]=[C:17]([O:20][CH3:21])[CH:18]=[CH:19][C:13]=3[C:12]=2[C:22](=[O:31])[C:23]2[CH:28]=[CH:27][C:26]([O:29][CH3:30])=[CH:25][CH:24]=2)=[CH:7][CH:6]=1
Reactant: COc1ccc(C(=O)Cl)cc1
Reactant: COc1ccc(-c2cc3ccc(OC)cc3s2)cc1
Agent: ClB(Cl)Cl
Agent: [Na+]
Agent: [OH-]
Solvent: CO
Solvent: ClCCl
Product: COc1ccc(C(=O)c2c(-c3ccc(OC)cc3)sc3cc(OC)ccc23)cc1
Yield: 89.6 %

Procedure:
A 250 mL, 3 neck, round bottomed flask fitted with a mechanical agitator and connected to a sodium hydroxide scrubber is purged with nitrogen and charged with 2-(4-methoxyphenyl)-6-methoxybenzo[b]thiophene (5.3 g, 19.6 mmol), p-anisoyl chloride (3.68 g, 21.56 mmol), and 100 mL of methylene chloride. To this slurry at 20° C. is added boron trichloride (3.4 mL, 39.8 mmol) which had been condensed in a graduated cylinder. The reaction mixture is quenched after 40 minutes by the slow addition of 50 mL of methanol over approximately 5 minutes followed by addition of 50 mL of water over 5 minutes. The organic phase is washed with 50 mL brine, dried over sodium sulfate, filtered, and concentrated affording a dark orange oil. Addition of 10 mL of methanol followed by sonication for 5 minutes resulted in crystallization of 7.1 g of crude product as a yellow solid. The crude material is recrystallized from 3:1 hexanes/toluene affording 5.9 g of product as pale yellow crystals. (75%).
Reaction SMILES: [CH2:1]([O:8][C:9](=[O:14])[C:10]([NH2:13])([CH3:12])[CH3:11])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[ClH:15].C([O:23][C:24](=O)[C@H:25](C)[NH:26]C(=O)CN)C1C=CC=CC=1>>[ClH:15].[CH2:1]([O:8][C:9](=[O:14])[C:10]([NH2:13])([CH3:11])[CH2:12][C:24](=[O:23])[CH2:25][NH2:26])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: CC(C)(N)C(=O)OCc1ccccc1
Reactant: C[C@H](NC(=O)CN)C(=O)OCc1ccccc1
Agent: Cl
Product: CC(N)(CC(=O)CN)C(=O)OCc1ccccc1

Procedure:
substitution of an equivalent amount of α-aminoisobutyric acid benzyl ester for the L-alanine benzyl ester of Example 3, and substantial repetition of the procedure detailed therein, affords glycyl-α-aminoisobutyric acid benzyl ester hydrochloride.
Reaction SMILES: [O:1]=[C:2]1[NH:6][C:5](=[O:7])[CH:4]([CH2:8][C:9]2[CH:46]=[CH:45][C:12]([O:13][CH2:14][C:15]([NH:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][C:25]4[CH:30]=[CH:29][C:28]([N:31]5[CH:35]=[CH:34][N:33]=[CH:32]5)=[CH:27][CH:26]=4)=[CH:20][C:19]=3[N:36]([CH3:44])C(=O)OC(C)(C)C)=O)=[CH:11][CH:10]=2)[S:3]1.[ClH:47].O1CCOCC1>>[ClH:47].[ClH:47].[N:31]1([C:28]2[CH:29]=[CH:30][C:25]([O:24][C:21]3[CH:22]=[CH:23][C:18]4[N:17]=[C:15]([CH2:14][O:13][C:12]5[CH:45]=[CH:46][C:9]([CH2:8][CH:4]6[S:3][C:2](=[O:1])[NH:6][C:5]6=[O:7])=[CH:10][CH:11]=5)[N:36]([CH3:44])[C:19]=4[CH:20]=3)=[CH:26][CH:27]=2)[CH:35]=[CH:34][N:33]=[CH:32]1
Reactant: CN(C(=O)OC(C)(C)C)c1cc(Oc2ccc(-n3ccnc3)cc2)ccc1NC(=O)COc1ccc(CC2SC(=O)NC2=O)cc1
Agent: Cl
Solvent: C1COCCO1
Product: Cn1c(COc2ccc(CC3SC(=O)NC3=O)cc2)nc2ccc(Oc3ccc(-n4ccnc4)cc3)cc21
Temperature: 25 °C
Reaction time: 19 h

Procedure:
A mixture of t-butyl N-{2-[4-(2,4-dioxothiazolidin-5-ylmethyl)phenoxyacetylamino]-5-[4-(imidazole-1-yl)phenoxy]phenyl}-N-methylcarbamate (1.75 g) and 4N hydrogen chloride/dioxane (20 ml) was stirred at ambient temperature for 19 hours. The solvent of the reaction mixture was evaporated to dryness. To the residue was added ethyl acetate and insoluble product was collected by filtration. The product was purified by reversed-phase high performance liquid chromatography using acetonitrile/water=7/13 as the eluant and was treated with 4N hydrogen chloride/acetate to give the title compound (0.20 g).
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[CH2:7]1[O:15][C:14]2[C:9](=[C:10]([OH:16])[CH:11]=[CH:12][CH:13]=2)[O:8]1.Cl[C:18]1[C:27]2[C:22](=[CH:23][C:24]([O:30][CH2:31][CH2:32][CH2:33][N:34]3[CH2:39][CH2:38][O:37][CH2:36][CH2:35]3)=[C:25]([O:28][CH3:29])[CH:26]=2)[N:21]=[CH:20][N:19]=1>CN(C=O)C.O>[CH3:29][O:28][C:25]1[CH:26]=[C:27]2[C:22](=[CH:23][C:24]=1[O:30][CH2:31][CH2:32][CH2:33][N:34]1[CH2:35][CH2:36][O:37][CH2:38][CH2:39]1)[N:21]=[CH:20][N:19]=[C:18]2[O:16][C:10]1[CH:11]=[CH:12][CH:13]=[C:14]2[O:15][CH2:7][O:8][C:9]=12
Reactant: COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
Reactant: Oc1cccc2c1OCO2
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CN(C)C=O
Product: COc1cc2c(Oc3cccc4c3OCO4)ncnc2cc1OCCCN1CCOCC1
Temperature: 25 °C
Reaction time: 0.17 h
Yield: 82 %

Procedure:
Potassium carbonate (0.092 g) was added to a solution of 2,3-methylenedioxyphenol (0.067 g) in DMF (3 ml) and the mixture was stirred at ambient temperature for 10 minutes. 4-Chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (0.15 g) was added and the mixture was heated to 70° C. for 3 hours. The mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with water and with brine, dried over magnesium sulphate and evaporated. There was thus obtained the title compound as a solid (0.16 g); NMR Spectrum: (DMSOd6 and CF3CO2D) 2.3 (m, 2H), 3.15 (m, 2H), 3.35 (m, 2H), 3.55 (d, 1H), 3.7 (t, 2H), 4.0 (s, 3H), 4.05 (m, 2H), 4.35 (t, 2H), 6.05 (s, 2H), 6.95 (m, 3H), 7.5 (s, 1H), 7.6 (s, 1H), 8.7 (s, 1H); Mass Spectrum: M+H+ 440; Elemental Analysis: Found C, 62.66; H, 5.78; N, 9.48; C23H25N3O6 requires C, 62.86; H, 5.73; N, 9.56%.
Reaction SMILES: [C:1]([CH2:3][C:4]([NH2:6])=[O:5])#[N:2].[C:7](OCC)(=[O:12])[CH2:8][C:9]([CH3:11])=O.[OH-].[K+]>CO>[C:1]([C:3]1[C:4]([OH:5])=[N:6][C:7]([OH:12])=[CH:8][C:9]=1[CH3:11])#[N:2]
Reactant: CCOC(=O)CC(C)=O
Reactant: N#CCC(N)=O
Agent: [K+]
Agent: [OH-]
Solvent: CO
Product: Cc1cc(O)nc(O)c1C#N
Temperature: 25 °C
Yield: 76.6 %

Procedure:
Cyanoacetamide (8, 34 g, 0.40 mol) and ethyl acetoacetate (9, 52 g, 0.40 mol) were dissolved in methanol (250 mL) at room temperature, a solution of potassium hydroxide (28 g, 0.42 mol) in methanol (200 mL) was slowly added, and the resulting mixture was heated to reflux for 12 h. The reaction mixture was cooled to room temperature and the white amorphous precipitate was filtered and washed with methanol (2×50 mL). The solid product was redissolved in hot water. The solution was carefully acidified and the off-white precipitate was allowed to form. The precipitate was filtered and washed with water and methanol to yield 110 (46 g, 75%): mp >300° C. (dec) [lit. (J. Org. Chem. 1960, 25, 560-564.) mp 315-320° C. (dee)]. 1H NMR (300 MHz, DMSO-d6) δ 5.58 (s, 1H), 2.22 (s, 3H).
Reaction SMILES: [C:1]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH2:12][C:13]#[N:14])[N:6]=1)(=[O:3])[CH3:2].[C:15](OC(=O)C)(=[O:17])[CH3:16].CO>O.N>[C:1]([NH:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([CH2:11][CH2:12][CH2:13][NH:14][C:15](=[O:17])[CH3:16])[N:6]=1)(=[O:3])[CH3:2]
Reactant: CC(=O)Nc1cccc(CCC#N)n1
Reactant: CC(=O)OC(C)=O
Agent: N
Solvent: O
Solvent: CO
Product: CC(=O)NCCCc1cccc(NC(C)=O)n1
Temperature: 25 °C
Reaction time: 28 h

Procedure:
2-Acetylamino-6-(2-cyanoethyl)pyridine (11.5 mg, 78 μmol) was dissolved in 25% ammonia water (3.0 ml) and, after purging with nitrogen, palladium black (30 mg) was added thereto. After repurging with nitrogen, the mixture was stirred at room temperature under a hydrogen stream at 9 atmospheres for 28 hours. After nitrogen purging, the palladium black was filtered off and the filtrate was concentrated under reduced pressure. Chloroform (500 μl) was added to the residue and, the mixture was cooled with ice and, after addition of acetic anhydride (100 μl, 1.1 mmol), stirred for 10 minutes. After allowing the temperature to rise to room temperature, stirring was continued for 5 hours. After cooling with ice, methanol (1.0 ml) was added and the mixture was stirred for 1 hour and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography [silica gel 10 g, chloroform-methanol (19:1)→(15:1)] to give 2-acetylamino-6-(3 -acetylaminopropyl)pyridine as a colorless solid (Yield 6 mg (51%)).
Reaction SMILES: [Li][CH2:2]CCC.[CH2:6]([C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[Se:21][CH:22]=[CH:23][CH:24]=3)=[C:16]([F:25])[CH:15]=2)=[CH:10][CH:9]=1)[CH3:7].CI.[Cl-].[NH4+].N>C(OCC)C>[CH2:6]([C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:19]=[CH:18][C:17]([C:20]3[Se:21][C:22]([CH3:2])=[CH:23][CH:24]=3)=[C:16]([F:25])[CH:15]=2)=[CH:12][CH:13]=1)[CH3:7]
Reactant: [Li]CCCC
Reactant: CCc1ccc(-c2ccc(-c3ccc[se]3)c(F)c2)cc1
Agent: N
Agent: [Cl-]
Agent: [NH4+]
Solvent: CCOCC
Solvent: CI
Product: CCc1ccc(-c2ccc(-c3ccc(C)[se]3)c(F)c2)cc1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
5.5 ml (32.3 mmol) of TMP are initially introduced at −15° C. in 20 ml of diethyl ether, and 20.0 ml (31.8 mmol, 15% soln. in hexane) of n-BuLi are metered in. After 30 min, a solution of 10.0 g (30.4 mmol) of 2-(4′-ethyl-3-fluorobiphenyl-4-yl)selenophene in 80 ml of diethyl ether is added. When the addition is complete, the batch is warmed to RT and stirred for 90 min. The solution is cooled to −70° C., and 10.0 ml (0.16 mol) of methyl iodide are added. The reaction mixture is warmed to RT and stirred for 20 h. Sat. ammonium chloride soln. and conc. ammonia soln. are added successively, and the mixture is stirred vigorously for a few minutes. The organic phase is separated off, and the aqueous phase is extracted with MTBE. The combined organic phases are washed successively with water, 2 N hydrochloric acid and sat. sodium chloride soln. The solution is dried using sodium sulfate and concentrated to dryness. The crude product is purified by column chromatography (SiO2, n-heptane:toluene=95:5). The further purification is carried out by recrystallisation from n-heptane. 2-(4′-Ethyl-3-fluorobiphenyl-4-yl)-5-methylselenophene is obtained as a solid having an m.p. of 121° C.
Reaction SMILES: [N:1]1[NH:2][N:3]=[N:4][C:5]=1[CH:6]1[CH2:11][CH2:10][N:9](C(OC(C)(C)C)=O)[CH2:8][CH2:7]1.[C:19]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O.CO>C1COCC1>[CH3:19][N:2]1[N:3]=[N:4][C:5]([CH:6]2[CH2:11][CH2:10][NH:9][CH2:8][CH2:7]2)=[N:1]1
Reactant: CC(C)(C)OC(=O)N1CCC(c2nn[nH]n2)CC1
Reactant: c1ccc(P(c2ccccc2)c2ccccc2)cc1
Agent: CC(C)OC(=O)N=NC(=O)OC(C)C
Solvent: CO
Solvent: C1CCOC1
Product: Cn1nnc(C2CCNCC2)n1
Reaction time: 0.17 h
Yield: 77.2 %

Procedure:
To a solution of tert-butyl 4-(2H-tetrazol-5-yl)piperidine-1-carboxylate (CAS 91419-58-8) (0.98 g, 3.89 mmol) and triphenylphosphine (3.06 g) in THF under a blanket of Ar was added the diisopropyl azodicarboxylate (2.30 ml) and the mixture stirred for 10 minutes. Methanol (473 μl) was added and the reaction was stirred for 18 hours and then the solution was concentrated in vacuo. The residue was purified on silica using a 90 g Biotage cartridge and a gradient elution of 25 to 35% ethyl acetate in hexanes. This semi-pure mixture was partially dissolved in a 4M HCl in dioxane solution and stirred for 1 hour, then concentrated in vacuo. The residue was partially dissolved in DCM (40 ml) and triethylamine (162 μl) and MP-Carbonate (4.17 g, loading 2.8 mmol/g) added and slurry stirred for 64 hours. The resin was filtered off and washed with a 10% solution of methanol in DCM and the filtrate was concentrated in vacuo. The residue was purified by column chromatography on SCX-2 stationary phase using methanol and then a 1M ammonia in methanol solution. Evaporation of the solvent under reduced pressure gave the title compound as a yellow solid (0.502 g); NMR (CDCl3): 1.78 (2H, m), 2.06 (2H, d), 2.77 (2H, m), 3.08 (1H, m), 3.19 (2H, d), 3.08 (3H, s).