Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl.Cl.[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][O:10][C:11](=[O:26])[C:12]1([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.[C:27]([O:31][C:32]([NH:34][C@H:35]([C:57](O)=[O:58])[CH2:36][S:37][C:38]([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)=[O:33])([CH3:30])([CH3:29])[CH3:28]>>[N:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[CH2:9][O:10][C:11](=[O:26])[C:12]1([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=2[CH3:25])[CH2:17][CH2:16][N:15]([C:57](=[O:58])[C@H:35]([CH2:36][S:37][C:38]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[NH:34][C:32]([O:31][C:27]([CH3:30])([CH3:28])[CH3:29])=[O:33])[CH2:14][CH2:13]1
Reactant: CC(C)(C)OC(=O)N[C@@H](CSC(c1ccccc1)(c1ccccc1)c1ccccc1)C(=O)O
Reactant: Cc1ccccc1CC1(C(=O)OCc2ccccn2)CCNCC1
Agent: Cl
Product: Cc1ccccc1CC1(C(=O)OCc2ccccn2)CCN(C(=O)[C@H](CSC(c2ccccc2)(c2ccccc2)c2ccccc2)NC(=O)OC(C)(C)C)CC1

Procedure:
4-(2-methylbenzyl)isonipecotic acid 2-pyridylmethyl ester bis HCl salt was coupled to N-t-butoxycarbonyl-S-trityl-L-Cysteine utilizing the procedure described in Example 1, Step 7 to afford the product as a white foam.
Reaction SMILES: O[CH2:2][CH2:3][CH2:4][NH:5][C:6](=[O:14])[C:7]1[CH:12]=[CH:11][C:10]([OH:13])=[CH:9][CH:8]=1>S(Cl)(Cl)=O>[O:14]1[CH2:2][CH2:3][CH2:4][N:5]=[C:6]1[C:7]1[CH:8]=[CH:9][C:10]([OH:13])=[CH:11][CH:12]=1
Reactant: O=C(NCCCO)c1ccc(O)cc1
Solvent: O=S(Cl)Cl
Product: Oc1ccc(C2=NCCCO2)cc1
Reaction time: 1.5 h
Yield: 29.7 %

Procedure:
A mixture of 37.8 g of N-(3-hydroxypropyl)-4-hydroxybenzamide and 100 ml of thionyl chloride was stirred for 1.5 hours. The reaction mixture was concentrated in vacuo, the solid residue triturated with ethyl acetate, and converted to the free base by treatment with ammonium hydroxide. There was obtained 10.2 g of 4-(5,6-dihydro-4H-1,3-oxazin-2-yl)phenol, m.p. 196°-198° C. (from methanol).
Reaction SMILES: CO[C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1.[NH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][OH:31]>>[OH:31][CH2:30][CH2:29][CH2:28][CH2:27][CH2:26][NH:25][C:3](=[O:24])[C:4]1[CH:9]=[CH:8][C:7]([O:10][CH2:11][C:12]2[C:13]([C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][CH:23]=3)=[N:14][O:15][C:16]=2[CH3:17])=[N:6][CH:5]=1
Reactant: COC(=O)c1ccc(OCc2c(-c3ccccc3)noc2C)nc1
Reactant: NCCCCCO
Product: Cc1onc(-c2ccccc2)c1COc1ccc(C(=O)NCCCCCO)cn1
Yield: 14 %

Procedure:
As described for example 220, 6-(5-methyl-3-phenyl-isoxazol-4-ylmethoxy)-nicotinic acid methyl ester (180 mg, 0.55 mmol) was converted, using 5-amino-1-pentanol instead of 3-amino-1-propanol, to the title compound (31 mg, 14%) which was obtained as a white solid. MS: m/e=396.1 [M+H]+.
Reaction SMILES: [N+:1]([C:4]1[CH:8]=[CH:7][N:6]([CH2:9][CH2:10][CH2:11][CH2:12][C:13]#[N:14])[N:5]=1)([O-:3])=[O:2].[OH-:15].[Na+]>S(=O)(=O)(O)O.O>[N+:1]([C:4]1[CH:8]=[CH:7][N:6]([CH2:9][CH2:10][CH2:11][CH2:12][C:13]([NH2:14])=[O:15])[N:5]=1)([O-:3])=[O:2]
Reactant: N#CCCCCn1ccc([N+](=O)[O-])n1
Reactant: [OH-]
Agent: O=S(=O)(O)O
Agent: [Na+]
Solvent: O
Product: NC(=O)CCCCn1ccc([N+](=O)[O-])n1

Procedure:
A solution of 5-(3-nitropyrazol-1-yl)valeronitrile (0.2 g.) in concentrated sulphuric acid (1 ml.) was kept at 20° for 19 hours. The mixture was diluted with water (4 ml.), basified to pH 10 with 10.8 N sodium hydroxide and extracted with EtOAc (3×5 ml.). The extracts were dried (MgSO4) and evaporated in vacuo to a white solid which was recrystallised from ethanol to give 5-(3-nitropyrazol-1-yl)valeramide, m.p. 129°-131°.
Reaction SMILES: Cl.[CH3:2][O:3][C:4](=[O:14])[CH:5]([NH2:13])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.[CH3:22][O:23][CH2:24][C:25](Cl)=[O:26].C(=O)(O)[O-].[Na+]>C(Cl)(Cl)Cl.O>[CH3:2][O:3][C:4](=[O:14])[C@@H:5]([NH:13][C:25](=[O:26])[CH2:24][O:23][CH3:22])[CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1
Reactant: COC(=O)C(N)Cc1ccccc1
Reactant: COCC(=O)Cl
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CCN(CC)CC
Solvent: O
Solvent: ClC(Cl)Cl
Product: COCC(=O)N[C@@H](Cc1ccccc1)C(=O)OC
Temperature: -78 °C
Yield: 73 %

Procedure:
500 mg of 2-amino-3-phenyl-propionic acid methylester hydrochloride dissolved in 10 ml of chloroform was cooled to −78° C., 0.96 ml of triethylamine and 0.23 ml of methoxyacetylchloride were added thereto, and the solution was reacted at room temperature for 2 hours. The reacted solution dissolved in distilled water was adjusted to pH 9 by adding saturated sodium bicarbonate solution, extracted with organic solvent, dried over magnesium sulfate, and filtered and distilled under a reduced pressure to obtain the title compound (427 mg, 73%).
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:12][C:11]([C:13](OCC)=[O:14])=[N:10][C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])=[CH:4][CH:3]=1.[NH2:26][N:27]1[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]1>ClCCl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[S:12][C:11]([C:13]([NH:26][N:27]3[CH2:32][CH2:31][CH2:30][CH2:29][CH2:28]3)=[O:14])=[N:10][C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[Cl:25])=[CH:6][CH:7]=1
Reactant: CCOC(=O)c1nc(-c2ccc(Cl)cc2Cl)c(-c2ccc(Br)cc2)s1
Reactant: NN1CCCCC1
Solvent: ClCCl
Product: O=C(NN1CCCCC1)c1nc(-c2ccc(Cl)cc2Cl)c(-c2ccc(Br)cc2)s1
Temperature: 50 °C
Yield: 78 %

Procedure:
Part E: A stirred mixture containing ethyl 5-(4-bromophenyl)-4-(2,4-dichlorophenyl)thiazole-2-carboxylate (1.00 gram, 2.2 mmol) and 1-aminopiperidine (10 mL) is heated overnight at 50° C. The resulting mixture is allowed to attain room temperature, dichloromethane is added and the resulting solution is twice washed with water, dried over MgSO4, filtered and concentrated in vacuo to give an oil. Flash chromatographic purification of this oil (ethyl acetate/petroleum ether=1/3 (v/v)) gives 5-(4-bromophenyl)-4-(2,4-dichlorophenyl)-N-(1-piperidinyl)thiazole-2-carboxamide (870 mg, 78% yield). Melting point: 171-173° C.
Reaction SMILES: CS(O[CH:6]1[CH2:10][CH:9]([C:11]2[N:15]3[C:16]4[CH:22]=[CH:21][N:20]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:17]=4[N:18]=[CH:19][C:14]3=[N:13][N:12]=2)[CH:8]([CH2:31][CH3:32])[CH2:7]1)(=O)=O.[N-:33]=[N+:34]=[N-:35].[Na+]>CN(C=O)C>[N:33]([CH:6]1[CH2:10][CH:9]([C:11]2[N:15]3[C:16]4[CH:22]=[CH:21][N:20]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:17]=4[N:18]=[CH:19][C:14]3=[N:13][N:12]=2)[CH:8]([CH2:31][CH3:32])[CH2:7]1)=[N+:34]=[N-:35]
Reactant: CCC1CC(OS(C)(=O)=O)CC1c1nnc2cnc3c(ccn3COCC[Si](C)(C)C)n12
Reactant: [N-]=[N+]=[N-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCC1CC(N=[N+]=[N-])CC1c1nnc2cnc3c(ccn3COCC[Si](C)(C)C)n12
Temperature: 25 °C
Reaction time: 20 h
Yield: 89.6 %

Procedure:
A round bottom flask was charged with 3-ethyl-4-(6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazin-1-yl)cyclopentyl methanesulfonate (0.83 g, 1.7 mmol, Preparation #IIII.1) and DMF (7.0 mL). To the reaction flask was added sodium azide (0.56 g, 8.6 mmol). The mixture was stirred at ambient temperature for about 20 h. Another portion of sodium azide (0.056 g, 0.86 mmol) was added and the reaction was stirred for about 2 h. The reaction was partitioned between EtOAc (20 mL) and water (20 mL). The layers were separated and the organic solution was dried over anhydrous MgSO4, filtered, and concentrated under reduced pressure to give 1-(-4-azido-2-ethylcyclopentyl)-6-((2-(trimethylsilyl)ethoxy)methyl)-6H-pyrrolo[2,3-e][1,2,4]triazolo[4,3-a]pyrazine (0.65 g, 88%) as a brown oil: LC/MS (Table 1, Method b) Rt=2.85 min; MS m/z: 427 (M+H)+.
Reaction SMILES: C[O:2][C:3](=[O:18])[CH2:4][C:5]1[CH:10]=[CH:9][C:8]([NH:11]C(=O)C)=[C:7]([N+:15]([O-:17])=[O:16])[CH:6]=1.[ClH:19]>>[ClH:19].[NH2:11][C:8]1[CH:9]=[CH:10][C:5]([CH2:4][C:3]([OH:18])=[O:2])=[CH:6][C:7]=1[N+:15]([O-:17])=[O:16]
Reactant: COC(=O)Cc1ccc(NC(C)=O)c([N+](=O)[O-])c1
Agent: Cl
Product: Nc1ccc(CC(=O)O)cc1[N+](=O)[O-]

Procedure:
A solution of (4-acetylamino-3-nitro-phenyl)-acetic acid methyl ester (1.3 g, 5.15 mmol) in 6 N aqueous hydrochloric acid (10 mL) was stirred at reflux for 1.5 h, then concentrated in vacuo to dryness. The residue was triturated with diethyl ether, filtered, washed with diethyl ether, and dried in vacuo to give 978 mg of product as a dark orange-yellow solid. 1H NMR 500 MHz (DMSO) δ 3.49 (s, 2H), 6.98 (d, 1H), 7.30 (dd, 1H), 7.86 (d, 1H); MS (m/z) 197 [M+H+]+.
Reaction SMILES: [C:1]([CH2:4][N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7](=[O:15])[C:6]1=[O:16])([OH:3])=[O:2].[CH3:17]O.S(=O)(=O)(O)O>O>[CH3:17][O:2][C:1]([CH2:4][N:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[NH:8][C:7](=[O:15])[C:6]1=[O:16])=[O:3]
Reactant: CO
Reactant: O=C(O)Cn1c(=O)c(=O)[nH]c2ccccc21
Agent: O=S(=O)(O)O
Solvent: O
Product: COC(=O)Cn1c(=O)c(=O)[nH]c2ccccc21
Temperature: 80 °C
Reaction time: 1 h
Yield: 21 %

Procedure:
A mixture of 1.0 g (4.5 mmol) 1-carboxymethylquinoxaline-2,3(1H,4H)-dione, 15 ml dry methanol and 0.2 ml concentrated sulfuric acid was stirred at 80° C. for 1 h. After cooling to 25° C. the reaction mixture was poured in water and made alkaline. The precipitate was filtered off and recrystallized (acetone) to give 0.22 g (21%) 1-methoxycarbonylmethylquinoxaline-2,3(1H,4H)-dione. M.p. 269° C. 1H-NMR (DMSO-d6): 12.0 (1H, broad s), 7.1 (4H, s), 4.9 (2H, s), 3.7 (3H, s).
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]([F:7])=[C:4]([F:6])[F:5].[CH2:10]([NH:12][CH2:13][CH3:14])[CH3:11]>C(Cl)Cl>[F:5][C:4]([N:12]([CH2:13][CH3:14])[CH2:10][CH3:11])([F:6])[CH:3]([F:7])[C:2]([F:9])([F:8])[F:1]
Reactant: CCNCC
Reactant: FC(F)=C(F)C(F)(F)F
Solvent: ClCCl
Product: CCN(CC)C(F)(F)C(F)C(F)(F)F
Temperature: 25 °C
Reaction time: 18 h
Yield: 75.7 %

Procedure:
Hexafluoropropylene (260 g; 1.73 mole) is bubbled into a solution of 287 ml (200 g; 2.74 mole) of diethylamine and 400 mL of methylene chloride over approximately 2 hours, keeping an internal temperature of about 10° with use of an ice bath. The reaction mixture is then stirred at room temperature for 18 hours. Low boiling compounds are removed by distillation at 70-80 mm and the product is distilled at 27°-32° C. and 8-10 mm, producing 238 ml (293 g; 1.31 mole) of N-(1,1,2,3,3,3-hexafluoropropyl)diethylamine.
Reaction SMILES: [H-].[Na+].[CH2:3]([OH:7])[C:4]#[C:5][CH3:6].Cl[C:9]1[CH:14]=[C:13]([O:15][CH:16]([CH3:21])[CH2:17][CH:18]([CH3:20])[CH3:19])[N:12]=[CH:11][N:10]=1.[Cl-].[NH4+]>O1CCCC1>[CH2:3]([O:7][C:9]1[CH:14]=[C:13]([O:15][CH:16]([CH3:21])[CH2:17][CH:18]([CH3:20])[CH3:19])[N:12]=[CH:11][N:10]=1)[C:4]#[C:5][CH3:6]
Reactant: CC#CCO
Reactant: CC(C)CC(C)Oc1cc(Cl)ncn1
Agent: [Cl-]
Agent: [H-]
Agent: [NH4+]
Solvent: C1CCOC1
Product: CC#CCOc1cc(OC(C)CC(C)C)ncn1
Reaction time: 0.17 h

Procedure:
In 3.5 ml of tetrahydrofuran was suspended 0.1 g of sodium hydride (60% in oil), to which 0.3 ml of a solution containing 0.16 g of 2-butyn-1-ol in tetrahydrofuran was added dropwise at room temperature, followed by stirring for 10 minutes. To this was added dropwise 0.3 ml of a solution containing the above 4-chloro-6-(1,3-dimethylbutoxy)pyrimidine in tetrahydrofuran, followed by stirring at room temperature for 4 hour. The reaction mixture was then poured into a saturated aqueous ammonium chloride solution, which was extracted three times with t-butyl methyl ether. The combined organic layers were washed with a saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The resulting residue was subjected to silica gel column chromatography to give 0.30 g of 4-(2-butynyloxy)-6-(1,3-dimethylbutyloxy)pyrimidine (the present compound (5)).
Reaction SMILES: [Br:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([OH:12])=O)=[CH:4][CH:3]=1.[B-](F)(F)(F)F.CCOC(C(C#N)=NOC(N(C)C)=[N+](C)C)=O.[NH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]1>CN(C=O)C>[Br:1][C:2]1[N:7]=[CH:6][C:5]([CH2:8][CH2:9][C:10]([N:35]2[CH2:40][CH2:39][CH2:38][CH2:37][CH2:36]2)=[O:12])=[CH:4][CH:3]=1
Reactant: C1CCNCC1
Reactant: O=C(O)CCc1ccc(Br)nc1
Agent: CCOC(=O)C(C#N)=NOC(N(C)C)=[N+](C)C
Agent: F[B-](F)(F)F
Solvent: CN(C)C=O
Product: O=C(CCc1ccc(Br)nc1)N1CCCCC1
Temperature: 25 °C
Reaction time: 0.25 h

Procedure:
9 g (39 mmol) of 3-(6-bromo-pyridin-3-yl)-propionic acid, 22.5 g (195 mmol) of NEM and 12.83 g (39 mmol) of TOTU were dissolved in 30 ml of DMF and stirred at room temperature for 15 min. 3.33 g (39 mmol) of piperidine were, and the reaction mixture was stirred at room temperature for 16 h. The solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with a saturated sodium hydrogencarbonate solution. The organic phase was dried with sodium sulfate, filtered, and the solvent was removed under reduced pressure. The product was purified by silica gel chromatography. Yield: 10.2 g.
Reaction SMILES: [CH2:1]([O:4][C:5]([NH:7][C:8]1[CH:9]=[C:10]([O:14][C:15](Cl)=[O:16])[CH:11]=[CH:12][CH:13]=1)=[O:6])[C:2]#[CH:3].[CH2:18]([NH:22][C:23]1[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=1)[CH:19]([CH3:21])[CH3:20].C(=O)([O-])[O-].[K+].[K+]>C(OC(=O)C)C.O>[CH2:1]([O:4][C:5]([NH:7][C:8]1[CH:9]=[C:10]([O:14][C:15](=[O:16])[N:22]([CH2:18][CH:19]([CH3:21])[CH3:20])[C:23]2[CH:28]=[CH:27][C:26]([CH3:29])=[CH:25][CH:24]=2)[CH:11]=[CH:12][CH:13]=1)=[O:6])[C:2]#[CH:3]
Reactant: C#CCOC(=O)Nc1cccc(OC(=O)Cl)c1
Reactant: Cc1ccc(NCC(C)C)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCOC(C)=O
Product: C#CCOC(=O)Nc1cccc(OC(=O)N(CC(C)C)c2ccc(C)cc2)c1
Temperature: 15 °C

Procedure:
A solution of 25.4 g (0.1 mol) of chloroformic acid-3-(2-propinyl-oxycarbonylamino)-phenylester in 100 ml acetic acid ethylester is added within a period of 20 minutes to a solution of 16.3 g (0.1 mol) of N-isobutyl-p-toluidine in 50 ml acetic acid ethylester. Simultaneously a solution of 13.8 g (0.1 mol) of potassium carbonate in 50 ml water is added dropwise while stirring and cooling to 15° C. temperature. Thereafter, the solution is further stirred at 15° C. for 30 minutes. The organic phase is then separated and washed at 0° C. with dilute sodium hydroxide, dilute hydrochloric acid and water. After drying on magnesium sulfate the mass is concentrated at a reduced pressure. It is then recrystallized from acetic acid ethylester/pentane.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13]([OH:16])=[CH:12][C:11]=2[S:17][CH3:18])=[O:9])=[CH:4][CH:3]=1.C([O-])([O-])=O.[K+].[K+].[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]Br>CC(C)=O>[Br:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][O:16][C:13]1[CH:14]=[CH:15][C:10]([C:8]([C:5]2[CH:6]=[CH:7][C:2]([Br:1])=[CH:3][CH:4]=2)=[O:9])=[C:11]([S:17][CH3:18])[CH:12]=1
Reactant: BrCCCCCCBr
Reactant: CSc1cc(O)ccc1C(=O)c1ccc(Br)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CC(C)=O
Product: CSc1cc(OCCCCCCBr)ccc1C(=O)c1ccc(Br)cc1

Procedure:
450 mg of (4-bromo-phenyl)-(4-hydroxy-2-methylsulphanyl-phenyl)-methanone are taken up in 7 ml of acetone and treated with 1.24 g of K2CO3 and 530 μl of 1,6-dibromohexane. The suspension is heated under reflux overnight, cooled, filtered and concentrated. After removing the excess 1,6-dibromohexane there are obtained 710 mg of [4-[6-(bromo)-hexyloxy]-2-methylsulphanyl-phenyl]-(4-bromo-phenyl)-methanone as a brown oil.
Reaction SMILES: [CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]2[N:10]=[C:11]3[CH:16]=[C:15]([C:17]#[N:18])[CH:14]=[CH:13][N:12]3[C:19]=2[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[CH:5][CH:4]=1)=O.C(N(CC)CC)C.Cl.Cl.[NH:35]1[CH2:40][CH2:39][CH:38]([C:41]2[N:45]=[C:44]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[O:43][N:42]=2)[CH2:37][CH2:36]1.C(O)(=O)C.[BH-](OC(C)=O)(OC(C)=O)OC(C)=O.[Na+]>C1COCC1.C(Cl)(Cl)Cl>[C:20]1([C:19]2[N:12]3[CH:13]=[CH:14][C:15]([C:17]#[N:18])=[CH:16][C:11]3=[N:10][C:9]=2[C:6]2[CH:5]=[CH:4][C:3]([CH2:1][N:35]3[CH2:40][CH2:39][CH:38]([C:41]4[N:45]=[C:44]([C:46]5[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=5)[O:43][N:42]=4)[CH2:37][CH2:36]3)=[CH:8][CH:7]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: N#Cc1ccn2c(-c3ccccc3)c(-c3ccc(C=O)cc3)nc2c1
Reactant: c1ccc(-c2nc(C3CCNCC3)no2)nc1
Agent: CC(=O)O[BH-](OC(C)=O)OC(C)=O
Agent: Cl
Agent: [Na+]
Solvent: CC(=O)O
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: N#Cc1ccn2c(-c3ccccc3)c(-c3ccc(CN4CCC(c5noc(-c6ccccn6)n5)CC4)cc3)nc2c1
Reaction time: 0.08 h

Procedure:
To a solution of 0.250 g (0.838 mM) of 2-(4-formylphenyl)-3-phenylimidazo[1,2-a]pyridine-7-carbonitrile in 6 mL of THF is added triethylamine (2 eq). The reaction mixture is stirred for 5 minutes. To this solution is added 2-[3-(piperidin-4-yl)-1,2,4-oxadiazol-5-yl]pyridine dihydrochloride (Intermediate L) (1.5 eq) followed by acetic acid (2.5 eq). The reaction mixture is stirred for 10 minutes. To this mixture is added NaBH(OAc)3 (6 eq) over a period of 40 minutes. The reaction mixture is stirred overnight. The reaction mixture is quenched with methanol and concentrated. The residue obtained is taken up in chloroform and washed with water, dried and concentrated. The crude is purified on a flash column chromatography to obtain the desired compound.
Reaction SMILES: ClC1C=C(C=CC=1)C(OO)=[O:6].[CH3:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([S:20][CH2:21][C:22]#[C:23][CH2:24][O:25][C:26]2[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=2)=[CH:16][CH:15]=1>C(Cl)(Cl)Cl>[CH3:12][O:13][C:14]1[CH:15]=[CH:16][C:17]2[S:20][CH2:21][CH:22]([C:23](=[O:6])[CH2:24][O:25][C:26]3[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=3)[C:18]=2[CH:19]=1
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: COc1ccc(SCC#CCOc2ccccc2)cc1
Solvent: ClC(Cl)Cl
Product: COc1ccc2c(c1)C(C(=O)COc1ccccc1)CS2
Temperature: 25 °C
Reaction time: 18 h

Procedure:
A solution of m-chloroperoxybenzoic acid (55% purity; 15.2 g) in chloroform (300 ml) was added dropwise over 2.5 hours to a stirred, ice-cold solution of 1-(4-methoxyphenylthio)-4-phenoxybut-2-yne(13.7 g) in chloroform (125 ml), then the mixture was stirred at ambient temperature for 18 hours and filtered. The filtrate was washed with 5% sodium carbonate solution (3×150 ml) and water (3×100 ml), then dried (MgSO4) and filtered. The filtrate was heated under nitrogen at an external temperature of 80°-85° C. for 6 hours, allowed to stand at ambient temperature for 18 hours, heated at an external temperature of 80°-85° C. for a further 1.5 hours, then allowed to cool. The solvent was removed in vacuo, the residue was dissolved in dichloromethane (250 ml), and the solution was shaken vigorously for a few seconds with 5M aqueous sodium hydroxide solution (150 ml). The organic solution was separated, washed with water (2×150 ml), dried (MgSO4), and the solvent removed in vacuo. The residue was purified by flash chromatography over silica using 12.5-25% mixtures of ethyl acetate and petroleum ether (b.p. 60°-80° C.) as eluants. Appropriate fractions were combined, and the solvents removed in vacuo to leave 1-(5-methoxy-2,3-dihydrobenzo[b]thiophen-3-yl)-2-phenoxyethanone as a gum (4.5 g).
Reaction SMILES: [CH:1]1[C@@H:6]([OH:7])[C@H:5]([OH:8])[C@H:4]([OH:9])[C@@H:3]([OH:10])[CH:2]=1.ClC1C=CC=C(C(OO)=[O:19])C=1>CO>[C@H:5]1([OH:8])[C@H:6]([OH:7])[C@@H:1]2[O:19][C@@H:2]2[C@H:3]([OH:10])[C@H:4]1[OH:9]
Reactant: O=C(OO)c1cccc(Cl)c1
Reactant: O[C@@H]1[C@H](O)[C@@H](O)C=C[C@H]1O
Solvent: CO
Product: O[C@@H]1[C@H](O)[C@@H](O)[C@H]2O[C@H]2[C@H]1O
Temperature: -20 °C
Yield: 45.1 %

Procedure:
800 mg of conduritol A and 1,448 mg of m-chloroperbenzoic acid were dissolved in 120 ml of methanol and the resultant mixture was stirred at room temperature for 4 days. Then, methanol was evaporated and the remaining residue was washed thrice with 80 ml of ether to remove chlorine compounds. Ether was removed off and the residue was then dissolved in as small amount of ethanol as possible, and allowed to crystallize by cooling to -20° C. The crystals were filtered with No. 2 filter paper and dried in a dessicator over night to give 400 mg of conduritol A epoxide.
Reaction SMILES: [C:1]([C:4]1[C:5]2[CH:13]=[CH:12][CH:11]=[C:10]([NH:14][C:15](=[O:24])[C:16]3[C:21]([Cl:22])=[CH:20][CH:19]=[CH:18][C:17]=3[Cl:23])[C:6]=2[O:7][C:8]=1[CH3:9])(=[O:3])[CH3:2].[CH3:25][Mg]Br.[Cl-].[NH4+].O>O1CCCC1>[Cl:22][C:21]1[CH:20]=[CH:19][CH:18]=[C:17]([Cl:23])[C:16]=1[C:15]([NH:14][C:10]1[C:6]2[O:7][C:8]([CH3:9])=[C:4]([C:1]([OH:3])([CH3:25])[CH3:2])[C:5]=2[CH:13]=[CH:12][CH:11]=1)=[O:24]
Reactant: CC(=O)c1c(C)oc2c(NC(=O)c3c(Cl)cccc3Cl)cccc12
Reactant: C[Mg]Br
Agent: [Cl-]
Agent: [NH4+]
Solvent: O
Solvent: C1CCOC1
Product: Cc1oc2c(NC(=O)c3c(Cl)cccc3Cl)cccc2c1C(C)(C)O
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a solution of 3-acetyl-7-(2,6-dichlorobenzoylamino)-2-methylbenzo[b]furan (100 mg) in tetrahydrofuran (3 ml) was added a 1M solution of methylmagnesium bromide in tetrahydrofuran (0.7 ml) dropwise with ice cooling. The solution was stirred at ambient temperature for 2 hours and to the solution was added aqueous saturated ammonium chloride. Then, the mixture was poured into water and the separated oil was extracted with ethyl acetate. The extract was washed with brine, dried over sodium sulfate and evaporated in vacuo. The residue was purified by colimn chromatography on silica gel and the obtained oil was crystallized from a mixture of diisopropyl ether and hexane to give 7-(2,6-dichlorobenzoylamino)-3-(1-hydroxy-1-methylethyl)-2-methylbenzo[b]furan (75 mg).
Reaction SMILES: [CH2:1]([O:3][C:4]([C@@H:6]1[CH2:11][CH2:10][C:9](=[O:12])[CH2:8][C@@H:7]1[CH2:13][CH2:14][CH2:15][CH3:16])=[O:5])[CH3:2].[CH2:17](O)[CH2:18][OH:19].C1(C)C=CC(S(O)(=O)=O)=CC=1.O>C1C=CC=CC=1.C(OCC)C>[CH2:1]([O:3][C:4]([C@H:6]1[CH2:11][CH2:10][C:9]2([O:19][CH2:18][CH2:17][O:12]2)[CH2:8][C@H:7]1[CH2:13][CH2:14][CH2:15][CH3:16])=[O:5])[CH3:2]
Reactant: CCCC[C@H]1CC(=O)CC[C@H]1C(=O)OCC
Reactant: OCCO
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CCOCC
Solvent: O
Solvent: c1ccccc1
Product: CCCC[C@@H]1CC2(CC[C@@H]1C(=O)OCC)OCCO2

Procedure:
cis-2-Butyl-4-oxocyclohexane carboxylic acid ethyl ester (9.0 g; 40 mmole), ethylene glycol (2.73 g; 44 mmole) and p-toluenesulphonic acid (100 mg) were refluxed in benzene 80 ml) using a Dean-Stark water trap. After 12 hours the mixture was cooled, diluted with diethyl ether and washed with saturated aqueous sodium bicarbonate followed by water. Drying over MgSO4 and evaporation gave a liquid (10.80 g; 100%) which was pure enough to use directly. Found: C, 66.71; H, 9.79. C15H26O4 requires C, 66.64; H, 9.69%.
Reaction SMILES: C(O)(=O)C(O)=O.[CH2:7]([NH:11][NH2:12])[CH2:8][CH2:9][CH3:10].O=[C:14]([CH2:20][C:21](=O)[CH3:22])[C:15]([O:17][CH2:18][CH3:19])=[O:16].C(N(CC)CC)C>C(O)C>[CH2:7]([N:11]1[C:21]([CH3:22])=[CH:20][C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:12]1)[CH2:8][CH2:9][CH3:10]
Reactant: CCOC(=O)C(=O)CC(C)=O
Reactant: CCCCNN
Agent: O=C(O)C(=O)O
Solvent: CCO
Solvent: CCN(CC)CC
Product: CCCCn1nc(C(=O)OCC)cc1C
Temperature: 25 °C
Reaction time: 8 h
Yield: 61.5 %

Procedure:
Butylhydrazine oxalate (25 g, 140 mmol) was added over a period of 15 minutes to a solution of ethyl 2,4-dioxovalerate (22.2 g, 140 mmol) and triethylamine (210 mmol) in ethanol (140 mL). The resulting solution was stirred overnight at ambient temperature and concentrated under reduced pressure. Hexane was added, and an insoluble solid was removed by filtration. The hexane was removed under reduced pressure; the residue was purified by chromatography on a HORIZON HPFC system (65I cartridge, eluting with hexanes/ethyl acetate in a gradient from 80:20 to 45:55) to provide 18.1 g of ethyl 1-butyl-5-methyl-1H-pyrazole-3-carboxylate as a pale yellow oil.